Wnt配体和受体在口腔鳞状细胞癌中的作用

穆罕默德·图法尔; 何彩云; 蒋灿华; 李宁

doi:10.1631/jzus.B2400251

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Wnt配体和受体在口腔鳞状细胞癌中的作用

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Review | Updated：2026-02-06

Wnt配体和受体在口腔鳞状细胞癌中的作用
Roles of Wnt ligands and receptors in oral squamous cell carcinoma
浙江大学学报（英文版）（B辑：生物医学和生物技术） 2026年27卷第2期页码：105-128
Affiliations：

1.Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha 410008, China
2.Institute of Oral Precancerous Lesions, Central South University, Changsha 410008, China
3.Research Center of Oral and Maxillofacial Tumor, Xiangya Hospital, Central South University, Changsha 410008, China
4.National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
Funds：

the National Natural Sciences Foundation of China(82170974);the Central South University Research Program of Advanced Interdisciplinary Studies(2023QYJC038)
DOI：10.1631/jzus.B2400251
中图分类号：
CSTR：
收稿：2024-05-20，

修回：2024-10-07，

网络首发：2025-11-21，

纸质出版：2026-02-06
Accepted：

穆罕默德·图法尔 ,何彩云,蒋灿华等.Wnt配体和受体在口腔鳞状细胞癌中的作用[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2026,27(02):105-128.

Muhammad TUFAIL, Caiyun HE, Canhua JIANG, et al. Roles of Wnt ligands and receptors in oral squamous cell carcinoma[J]. Journal of Zhejiang University-SCIENCE B, 2026, 27(2): 105-128.
穆罕默德·图法尔 ,何彩云,蒋灿华等.Wnt配体和受体在口腔鳞状细胞癌中的作用[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2026,27(02):105-128. DOI： 10.1631/jzus.B2400251.

Muhammad TUFAIL, Caiyun HE, Canhua JIANG, et al. Roles of Wnt ligands and receptors in oral squamous cell carcinoma[J]. Journal of Zhejiang University-SCIENCE B, 2026, 27(2): 105-128. DOI： 10.1631/jzus.B2400251.

摘要

口腔鳞状细胞癌（OSCC）具有较高发病率和死亡率，在临床诊断和治疗中面临重大挑战。最新研究证实Wnt配体及其受体在OSCC发病中具有关键作用。Wnt信号通路失调可通过促进细胞增殖和上皮-间质转化（EMT），以及维持癌症干细胞（CSC）干性，来驱动肿瘤的发生与发展，并导致其产生治疗抵抗。尽管靶向Wnt信号通路展现出潜在的治疗前景，但要实现有效干预，仍需对Wnt与其他信号通路的复杂相互作用展开进一步研究。本文对Wnt配体和受体在OSCC中作用的最新研究进行综述，强调其作为诊断生物标志物和治疗靶点的潜力。未来的研究方向包括阐明Wnt信号通路在特定背景下的动态变化，并探索联合疗法以提高OSCC患者的临床治疗效果。

Abstract

Oral squamous cell carcinoma (OSCC) poses significant challenges in terms of diagnosis and treatment

with high rates of morbidity and mortality. Emerging evidence highlights the critical involvement of Wingless/Int-1 (Wnt) ligands and receptors in OSCC pathogenesis. Dysregulated Wnt signaling pathways contribute to tumor initiation

progression

and therapy resistance by promoting cellular proliferation

epithelial‒mesenchymal transition (EMT)

and the maintenance of cancer stem cells (CSCs). Targeting Wnt signaling presents a promising therapeutic avenue

yet its complex interplay with other signaling pathways requires a deeper understanding to implement effective intervention. This study sheds light on the current knowledge of the roles of Wnt ligands and receptors in OSCC

emphasizing their potential as diagnostic biomarkers and therapeutic targets. Future research directions involve elucidating context-specific Wnt signaling dynamics and exploring combination therapies to improve clinical outcomes for OSCC patients.

关键词

Keywords

references

Ai YL , Wu SY , Zou C , et al. , 2020 . LINC00941 promotes oral squamous cell carcinoma progression via activating CAPRIN2 and canonical WNT/β-catenin signaling pathway . J Cell Mol Med , 24 ( 18 ): 10512 - 10524 . https://doi.org/10.1111/jcmm.15667 https://doi.org/10.1111/jcmm.15667

Arebro J , Towle R , Lee CM , et al. , 2023 . Extracellular vesicles promote activation of pro-inflammatory cancer-associated fibroblasts in oral cancer . Front Cell Dev Biol , 11 : 1240159 . https://doi.org/10.3389/fcell.2023.1240159 https://doi.org/10.3389/fcell.2023.1240159

Bai YP , Sha JJ , Kanno T , 2020 . The role of carcinogenesis-related biomarkers in the Wnt pathway and their effects on epithelial‒mesenchymal transition (EMT) in oral squamous cell carcinoma . Cancers , 12 ( 3 ): 555 . https://doi.org/10.3390/cancers12030555 https://doi.org/10.3390/cancers12030555

Bais MV , Kukuruzinska M , Trackman PC , 2015 . Orthotopic non-metastatic and metastatic oral cancer mouse models . Oral Oncol , 51 ( 5 ): 476 - 482 . https://doi.org/10.1016/j.oraloncology.2015.01.012 https://doi.org/10.1016/j.oraloncology.2015.01.012

Bueno MLP , Saad STO , Roversi FM , 2022 . WNT5A in tumor development and progression: a comprehensive review . Biomed Pharmacother , 155 : 113599 . https://doi.org/10.1016/j.biopha.2022.113599 https://doi.org/10.1016/j.biopha.2022.113599

Cadena IA , Buchanan MR , Harris CG , et al. , 2023 . Engineering high throughput screening platforms of cervical cancer . J Biomed Mater Res , 111 ( 6 ): 747 - 764 . https://doi.org/10.1002/jbm.a.37522 https://doi.org/10.1002/jbm.a.37522

Cadigan KM , Waterman ML , 2012 . TCF/LEFs and Wnt signaling in the nucleus . Cold Spring Harb Perspect Biol , 4 ( 11 ): a007906 . https://doi.org/10.1101/cshperspect.a007906 https://doi.org/10.1101/cshperspect.a007906

Chandler KB , Alamoud KA , Stahl VL , et al. , 2020 . β-Catenin/CBP inhibition alters epidermal growth factor receptor fucosylation status in oral squamous cell carcinoma . Mol Omics , 16 ( 3 ): 195 - 209 . https://doi.org/10.1039/d0mo00009d https://doi.org/10.1039/d0mo00009d

Chaves P , Garrido M , Oliver J , et al. , 2023 . Preclinical models in head and neck squamous cell carcinoma . Br J Cancer , 128 ( 10 ): 1819 - 1827 . https://doi.org/10.1038/s41416-023-02186-1 https://doi.org/10.1038/s41416-023-02186-1

Chen C , Luo LN , Xu CL , et al. , 2022 . Tumor specificity of WNT ligands and receptors reveals universal squamous cell carcinoma oncogenes . BMC Cancer , 22 : 790 . https://doi.org/10.1186/s12885-022-09898-2 https://doi.org/10.1186/s12885-022-09898-2

Cierpikowski P , Lis-Nawara A , Bar J , 2023 . Prognostic value of WNT1, NOTCH1, PDGFRβ, and CXCR4 in oral squamous cell carcinoma . Anticancer Res , 43 ( 2 ): 591 - 602 . https://doi.org/10.21873/anticanres.16195 https://doi.org/10.21873/anticanres.16195

Dalir Abdolahinia E , Han XZ , 2023 . The three-dimensional in vitro cell culture models in the study of oral cancer immune microenvironment . Cancers , 15 ( 17 ): 4266 . https://doi.org/10.3390/cancers15174266 https://doi.org/10.3390/cancers15174266

Dong Y , Zhao Q , Ma XY , et al. , 2015 . Establishment of a new OSCC cell line derived from OLK and identification of malignant transformation-related proteins by differential proteomics approach . Sci Rep , 5 : 12668 . https://doi.org/10.1038/srep12668 https://doi.org/10.1038/srep12668

Farrapo MT , Rifane TO , Pinto DN , et al. , 2022 . Canonical WNT signaling pathway in oral squamous cell carcinoma prognosis . Res Soc Dev , 11 ( 2 ): e8411225462 . https://doi.org/10.33448/rsd-v11i2.25462 https://doi.org/10.33448/rsd-v11i2.25462

Farshbaf A , Lotfi M , Zare R , et al. , 2023 . The organoid as reliable cancer modeling in personalized medicine, does applicable in precision medicine of head and neck squamous cell carcinoma? Pharmacogenomics J , 23 ( 2-3 ): 37 - 44 . https://doi.org/10.1038/s41397-022-00296-2 https://doi.org/10.1038/s41397-022-00296-2

Fleming-de-Moraes CD , Rocha MR , Tessmann JW , et al. , 2022 . Crosstalk between PI3K/Akt and Wnt/β-catenin pathways promote colorectal cancer progression regardless of mutational status . Cancer Biol Ther , 23 ( 1 ): 1 - 13 . https://doi.org/10.1080/15384047.2022.2108690 https://doi.org/10.1080/15384047.2022.2108690

Ge C , Huang XT , Zhang SJ , et al. , 2023 . In vitro co-culture systems of hepatic and intestinal cells for cellular pharmacokinetic and pharmacodynamic studies of capecitabine against colorectal cancer . Cancer Cell Int , 23 : 14 . https://doi.org/10.1186/s12935-023-02853-6 https://doi.org/10.1186/s12935-023-02853-6

Grimaldi M , Boulahtouf A , Prévostel C , et al. , 2018 . A cell model suitable for a high-throughput screening of inhibitors of the Wnt/β-catenin pathway . Front Pharmacol , 9 : 1160 . https://doi.org/10.3389/fphar.2018.01160 https://doi.org/10.3389/fphar.2018.01160

He K , Gan WJ , 2023 . Wnt/β-catenin signaling pathway in the development and progression of colorectal cancer . Cancer Manag Res , 15 : 435 - 448 . https://doi.org/10.2147/cmar.S411168 https://doi.org/10.2147/cmar.S411168

Hou ZY , Wu CZ , Tang JR , et al. , 2024 . CLSPN actives Wnt/β-catenin signaling to facilitate glycolysis and cell proliferation in oral squamous cell carcinoma . Exp Cell Res , 435 ( 2 ): 113935 . https://doi.org/10.1016/j.yexcr.2024.113935 https://doi.org/10.1016/j.yexcr.2024.113935

Hsu TN , Huang CM , Huang CS , et al. , 2019 . Targeting FAT1 inhibits carcinogenesis, induces oxidative stress and enhances cisplatin sensitivity through deregulation of LRP5/WNT2/GSS signaling axis in oral squamous cell carcinoma . Cancers , 11 ( 12 ): 1883 . https://doi.org/10.3390/cancers11121883 https://doi.org/10.3390/cancers11121883

Hsueh PC , Chang KP , Liu HP , et al. , 2022 . Development of a salivary autoantibody biomarker panel for diagnosis of oral cavity squamous cell carcinoma . Front Oncol , 12 : 968570 . https://doi.org/10.3389/fonc.2022.968570 https://doi.org/10.3389/fonc.2022.968570

Invrea F , Rovito R , Torchiaro E , et al. , 2020 . Patient-derived xenografts (PDXs) as model systems for human cancer . Curr Opin Biotechnol , 63 : 151 - 156 . https://doi.org/10.1016/j.copbio.2020.01.003 https://doi.org/10.1016/j.copbio.2020.01.003

Jia B , Qiu XL , Chu HX , et al. , 2019 . Wnt7a predicts poor prognosis, and contributes to growth and metastasis in tongue squamous cell carcinoma . Oncol Rep , 41 ( 3 ): 1749 - 1758 . https://doi.org/10.3892/or.2019.6974 https://doi.org/10.3892/or.2019.6974

Joiner DM , Ke JY , Zhong ZD , et al. , 2013 . LRP5 and LRP6 in development and disease . Trends Endocrinol Metab , 24 ( 1 ): 31 - 39 . https://doi.org/10.1016/j.tem.2012.10.003 https://doi.org/10.1016/j.tem.2012.10.003

Jung EK , Kim SA , Yoon TM , et al. , 2017 . WNT1-inducible signaling pathway protein-1 contributes to tumor progression and treatment failure in oral squamous cell carcinoma . Oncol Lett , 14 ( 2 ): 1719 - 1724 . https://doi.org/10.3892/ol.2017.6313 https://doi.org/10.3892/ol.2017.6313

Kalinke LP , Alvares LE , Schussel JL , et al. , 2016 . Expression of WNT10A gene in oral squamous cell carcinoma . West Indian Med J , 65 ( 3 ): 480 - 485 . https://doi.org/10.7727/wimj.2014.347 https://doi.org/10.7727/wimj.2014.347

Kartha VK , Alamoud KA , Sadykov K , et al. , 2018 . Functional and genomic analyses reveal therapeutic potential of targeting β-catenin/CBP activity in head and neck cancer . Genome Med , 10 : 54 . https://doi.org/10.1186/s13073-018-0569-7 https://doi.org/10.1186/s13073-018-0569-7

Kayamori K , Katsube KI , Hirai H , et al. , 2023 . Role of stromal fibroblast-induced WNT7A associated with cancer cell migration through the AKT/CLDN1 signaling axis in oral squamous cell carcinoma . Lab Invest , 103 ( 10 ): 100228 . https://doi.org/10.1016/j.labinv.2023.100228 https://doi.org/10.1016/j.labinv.2023.100228

Kim O , Ahn K , Kim HE , et al. , 2019 . Screening of β-catenin inhibitor from medicinal plant extracts for intractable recurrent oral cancer . Oral Surg Oral Med Oral Pathol Oral Radiol , 128 ( 1 ): e43 . https://doi.org/10.1016/j.oooo.2019.02.086 https://doi.org/10.1016/j.oooo.2019.02.086

Krisanaprakornkit S , Iamaroon A , 2012 . Epithelial-mesenchymal transition in oral squamous cell carcinoma . Int Scholarly Res Not , 2012 : 681469 . https://doi.org/10.5402/2012/681469 https://doi.org/10.5402/2012/681469

Kumar V , Vashishta M , Kong L , et al. , 2021 . The role of notch, hedgehog, and Wnt signaling pathways in the resistance of tumors to anticancer therapies . Front Cell Dev Biol , 9 : 650772 . https://doi.org/10.3389/fcell.2021.650772 https://doi.org/10.3389/fcell.2021.650772

Lau HK , Wu ER , Chen MK , et al. , 2017 . Effect of genetic variation in microRNA binding site in WNT1-inducible signaling pathway protein 1 gene on oral squamous cell carcinoma susceptibility . PLoS ONE , 12 ( 4 ): e0176246 . https://doi.org/10.1371/journal.pone.0176246 https://doi.org/10.1371/journal.pone.0176246

Lee G , Kim YB , Kim JH , et al. , 2002 . Characterization of novel cell lines established from three human oral squamous cell carcinomas . Int J Oncol , 20 ( 6 ): 1151 - 1159 .

Lee SY , Koo IS , Hwang HJ , et al. , 2023 . In vitro three-dimensional (3D) cell culture tools for spheroid and organoid models . SLAS Discov , 28 ( 4 ): 119 - 137 . https://doi.org/10.1016/j.slasd.2023.03.006 https://doi.org/10.1016/j.slasd.2023.03.006

Li Q , Dong H , Yang GW , et al. , 2020 . Mouse tumor-bearing models as preclinical study platforms for oral squamous cell carcinoma . Front Oncol , 10 : 212 . https://doi.org/10.3389/fonc.2020.00212 https://doi.org/10.3389/fonc.2020.00212

Liu BY , Chen W , Cao G , et al. , 2017 . MicroRNA-27b inhibits cell proliferation in oral squamous cell carcinoma by targeting FZD7 and Wnt signaling pathway . Arch Oral Biol , 83 : 92 - 96 . https://doi.org/10.1016/j.archoralbio.2017.07.009 https://doi.org/10.1016/j.archoralbio.2017.07.009

Liu BY , Cao G , Dong Z , et al. , 2019 . Effect of microRNA-27b on cisplatin chemotherapy sensitivity of oral squamous cell carcinoma via FZD7 signaling pathway . Oncol Lett , 18 ( 1 ): 667 - 673 . https://doi.org/10.3892/ol.2019.10347 https://doi.org/10.3892/ol.2019.10347

Liu J , Pan SF , Hsieh MH , et al. , 2013 . Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974 . Proc Natl Acad Sci USA , 110 ( 50 ): 20224 - 20229 . https://doi.org/10.1073/pnas.1314239110 https://doi.org/10.1073/pnas.1314239110

Liu LJ , Jiang H , Zhao J , et al. , 2018 . MiRNA-16 inhibited oral squamous carcinoma tumor growth in vitro and in vivo via suppressing Wnt/β-catenin signaling pathway . Onco Targets Ther , 11 : 5111 - 5119 . https://doi.org/10.2147/OTT.S153888 https://doi.org/10.2147/OTT.S153888

Liu YH , Wu WT , Cai CJ , et al. , 2023 . Patient-derived xenograft models in cancer therapy: technologies and applications . Signal Transduct Target Ther , 8 : 160 . https://doi.org/10.1038/s41392-023-01419-2 https://doi.org/10.1038/s41392-023-01419-2

Ma JT , Ren YP , Zhang L , et al. , 2017 . Knocking-down of CREPT prohibits the progression of oral squamous cell carcinoma and suppresses cyclin D1 and c-Myc expression . PLoS ONE , 12 ( 4 ): e0174309 . https://doi.org/10.1371/journal.pone.0174309 https://doi.org/10.1371/journal.pone.0174309

Mehterov N , Vladimirov B , Sacconi A , et al. , 2021 . Salivary miR-30c-5p as potential biomarker for detection of oral squamous cell carcinoma . Biomedicines , 9 ( 9 ): 1079 . https://doi.org/10.3390/biomedicines9091079 https://doi.org/10.3390/biomedicines9091079

Meng X , Lou QY , Yang WY , et al. , 2021 . The role of non-coding RNAs in drug resistance of oral squamous cell carcinoma and therapeutic potential . Cancer Commun (Lond) , 41 ( 10 ): 981 - 1006 . https://doi.org/10.1002/cac2.12194 https://doi.org/10.1002/cac2.12194

Menon R , Li CC , Li MZ , 2017 . Wnt signaling in oral cancer initiating cells . Oral Surg Oral Med Oral Pathol Oral Radiol , 124 ( 3 ): e202 . https://doi.org/10.1016/j.oooo.2017.06.015 https://doi.org/10.1016/j.oooo.2017.06.015

Millen R , de Kort WWB , Koomen M , et al. , 2023 . Patient-derived head and neck cancer organoids allow treatment stratification and serve as a tool for biomarker validation and identification . Med , 4 ( 5 ): 290 - 310.e12 . https://doi.org/10.1016/j.medj.2023.04.003 https://doi.org/10.1016/j.medj.2023.04.003

Min AJ , Zhu C , Peng SP , et al. , 2016 . Downregulation of microRNA-148a in cancer-associated fibroblasts from oral cancer promotes cancer cell migration and invasion by targeting Wnt10b . J Biochem Mol Toxicol , 30 ( 4 ): 186 - 191 . https://doi.org/10.1002/jbt.21777 https://doi.org/10.1002/jbt.21777

Ngernsombat C , Prattapong P , Larbcharoensub N , et al. , 2021 . WNT8B as an independent prognostic marker for nasopharyngeal carcinoma . Curr Oncol , 28 ( 4 ): 2529 - 2539 . https://doi.org/10.3390/curroncol28040230 https://doi.org/10.3390/curroncol28040230

Nguyen NT , Doan VN , Tran HLB , 2023 . Role of co-culture with fibroblasts and dynamic culture systems in 3-dimensional MCF-7 tumor model maturation . Trends Sci , 20 ( 2 ): 3892 - 3892 . https://doi.org/10.48048/tis.2023.3892 https://doi.org/10.48048/tis.2023.3892

Nie XB , Liu HY , Liu L , et al. , 2020 . Emerging roles of Wnt ligands in human colorectal cancer . Front Oncol , 10 : 1341 . https://doi.org/10.3389/fonc.2020.01341 https://doi.org/10.3389/fonc.2020.01341

Noguti J , de Moura CFG , Hossaka TA , et al. , 2012 . The role of canonical WNT signaling pathway in oral carcinogenesis: a comprehensive review . Anticancer Res , 32 ( 3 ): 873 - 878 .

Paluszczak J , 2020 . The significance of the dysregulation of canonical Wnt signaling in head and neck squamous cell carcinomas . Cells , 9 ( 3 ): 723 . https://doi.org/10.3390/cells9030723 https://doi.org/10.3390/cells9030723

Patel S , Alam A , Pant R , et al. , 2019 . Wnt signaling and its significance within the tumor microenvironment: novel therapeutic insights . Front Immunol , 10 : 2872 . https://doi.org/10.3389/fimmu.2019.02872 https://doi.org/10.3389/fimmu.2019.02872

Patil DJ , Nagaraju R , 2021 . Personalised precision medicine - a novel approach for oral cancer management . In: Sridharan G (Ed.), Oral Cancer—Current Concepts and Future Perspectives . IntechOpen, Rijeka. https://doi.org/10.5772/intechopen.99558 https://doi.org/10.5772/intechopen.99558

Pekarek L , Garrido-Gil MJ , Sánchez-Cendra A , et al. , 2023 . Emerging histological and serological biomarkers in oral squamous cell carcinoma: applications in diagnosis, prognosis evaluation and personalized therapeutics (Review) . Oncol Rep , 50 ( 6 ): 213 . https://doi.org/10.3892/or.2023.8650 https://doi.org/10.3892/or.2023.8650

Peña-Oyarzún D , Flores T , Torres VA , et al. , 2024 . Inhibition of PORCN blocks Wnt signaling to attenuate progression of oral carcinogenesis . Clin Cancer Res , 30 ( 1 ): 209 - 223 . https://doi.org/10.1158/1078-0432.CCR-23-0318 https://doi.org/10.1158/1078-0432.CCR-23-0318

Prgomet Z , Lindberg P , Andersson T , 2013 . PP064: Wnt5a stimulates migration and invasion in OSCC . Oral Oncol , 49 ( suppl 1 ): S115 - S116 . https://doi.org/10.1016/j.oraloncology.2013.03.307 https://doi.org/10.1016/j.oraloncology.2013.03.307

Prgomet Z , Andersson T , Lindberg P , 2017 . Higher expression of WNT5A protein in oral squamous cell carcinoma compared with dysplasia and oral mucosa with a normal appearance . Eur J Oral Sci , 125 ( 4 ): 237 - 246 . https://doi.org/10.1111/eos.12352 https://doi.org/10.1111/eos.12352

Prossomariti A , Piazzi G , Alquati C , et al. , 2020 . Are Wnt/β-catenin and PI3K/AKT/mTORC1 distinct pathways in colorectal cancer? Cell Mol Gastroenterol Hepatol , 10 ( 3 ): 491 - 506 . https://doi.org/10.1016/j.jcmgh.2020.04.007 https://doi.org/10.1016/j.jcmgh.2020.04.007

Purwaningsih NMS , Khor GH , Nik Mohd Rosdy NMM , et al. , 2021 . Wnt pathway in oral cancer: a review update . Saudi Dent J , 33 ( 8 ): 813 - 818 . https://doi.org/10.1016/j.sdentj.2021.08.002 https://doi.org/10.1016/j.sdentj.2021.08.002

Ren Q , Chen JC , Liu YH , 2021 . LRP5 and LRP6 in Wnt signaling: similarity and divergence . Front Cell Dev Biol , 9 : 670960 . https://doi.org/10.3389/fcell.2021.670960 https://doi.org/10.3389/fcell.2021.670960

Reyes M , Flores T , Betancur D , et al. , 2020 . Wnt/β-catenin signaling in oral carcinogenesis . Int J Mol Sci , 21 ( 13 ): 4682 . https://doi.org/10.3390/ijms21134682 https://doi.org/10.3390/ijms21134682

Robert BM , Dakshinamoorthy M , Ganapathyagraharam Ramamoorthy B , et al. , 2018 . Predicting tumor sensitivity to chemotherapeutic drugs in oral squamous cell carcinoma patients . Sci Rep , 8 : 15545 . https://doi.org/10.1038/s41598-018-33998-4 https://doi.org/10.1038/s41598-018-33998-4

Roslan Z , Muhamad M , Selvaratnam L , et al. , 2019 . The roles of low-density lipoprotein receptor-related proteins 5, 6, and 8 in cancer: a review . J Oncol , 2019 : 4536302 . https://doi.org/10.1155/2019/4536302 https://doi.org/10.1155/2019/4536302

Sa P , Singh P , Panda S , et al. , 2024 . Reversal of cisplatin resistance in oral squamous cell carcinoma by piperlongumine loaded smart nanoparticles through inhibition of Hippo-YAP signaling pathway . Transl Res , 268 : 63 - 78 . https://doi.org/10.1016/j.trsl.2024.03.004 https://doi.org/10.1016/j.trsl.2024.03.004

Sajeev A , BharathwajChetty B , Vishwa R , et al. , 2023 . Crosstalk between non-coding RNAs and Wnt/β-catenin signaling in head and neck cancer: identification of novel biomarkers and therapeutic agents . Non-coding RNA , 9 ( 5 ): 63 . https://doi.org/10.3390/ncrna9050063 https://doi.org/10.3390/ncrna9050063

Sakamoto T , Kawano S , Matsubara R , et al. , 2017 . Critical roles of Wnt5a‒Ror2 signaling in aggressiveness of tongue squamous cell carcinoma and production of matrix metalloproteinase-2 via ΔNp63β-mediated epithelial-mesenchymal transition . Oral Oncol , 69 : 15 - 25 . https://doi.org/10.1016/j.oraloncology.2017.03.019 https://doi.org/10.1016/j.oraloncology.2017.03.019

Shen YH , Chen YL , Lin YT , et al. , 2023 . CDK5RAP2 is a Wnt target gene and promotes stemness and progression of oral squamous cell carcinoma . Cell Death Dis , 14 ( 2 ): 107 . https://doi.org/10.1038/s41419-023-05652-z https://doi.org/10.1038/s41419-023-05652-z

Shiah SG , Shieh YS , Chang JY , 2015 . The role of Wnt signaling in squamous cell carcinoma . J Dent Res , 95 ( 2 ): 129 - 134 . https://doi.org/10.1177/0022034515613507 https://doi.org/10.1177/0022034515613507

Silva JPN , Pinto B , Monteiro L , et al. , 2023 . Combination therapy as a promising way to fight oral cancer . Pharmaceutics , 15 ( 6 ): 1653 . https://doi.org/10.3390/pharmaceutics15061653 https://doi.org/10.3390/pharmaceutics15061653

Silveira FM , Schmidt TR , Neumann B , et al. , 2023 . Impact of photobiomodulation in a patient-derived xenograft model of oral squamous cell carcinoma . Oral Dis , 29 ( 2 ): 547 - 556 . https://doi.org/10.1111/odi.13967 https://doi.org/10.1111/odi.13967

Smith AJ , Sompel KM , Elango A , et al. , 2021 . Non-coding RNA and frizzled receptors in cancer . Front Mol Biosci , 8 : 712546 . https://doi.org/10.3389/fmolb.2021.712546 https://doi.org/10.3389/fmolb.2021.712546

Sompel K , Elango A , Smith AJ , et al. , 2021 . Cancer chemoprevention through Frizzled receptors and EMT . Discov Oncol , 12 : 32 . https://doi.org/10.1007/s12672-021-00429-2 https://doi.org/10.1007/s12672-021-00429-2

Srivastava G , Matta A , Fu GD , et al. , 2015 . Anticancer activity of pyrithione zinc in oral cancer cells identified in small molecule screens and xenograft model: implications for oral cancer therapy . Mol Oncol , 9 ( 8 ): 1720 - 1735 . https://doi.org/10.1016/j.molonc.2015.05.005 https://doi.org/10.1016/j.molonc.2015.05.005

Sun LL , Kang XD , Wang C , et al. , 2023 . Single-cell and spatial dissection of precancerous lesions underlying the initiation process of oral squamous cell carcinoma . Cell Discov , 9 : 28 . https://doi.org/10.1038/s41421-023-00532-4 https://doi.org/10.1038/s41421-023-00532-4

Takabatake K , Kawai H , Omori H , et al. , 2020 . Impact of the stroma on the biological characteristics of the parenchyma in oral squamous cell carcinoma . Int J Mol Sci , 21 ( 20 ): 7714 . https://doi.org/10.3390/ijms21207714 https://doi.org/10.3390/ijms21207714

Takeshita A , Iwai S , Morita Y , et al. , 2014 . Wnt5b promotes the cell motility essential for metastasis of oral squamous cell carcinoma through active Cdc42 and RhoA . Int J Oncol , 44 ( 1 ): 59 - 68 . https://doi.org/10.3892/ijo.2013.2172 https://doi.org/10.3892/ijo.2013.2172

Tan YH , Wang ZH , Xu MT , et al. , 2023 . Oral squamous cell carcinomas: state of the field and emerging directions . Int J Oral Sci , 15 : 44 . https://doi.org/10.1038/s41368-023-00249-w https://doi.org/10.1038/s41368-023-00249-w

Tasoulas J , Srivastava S , Xu XN , et al. , 2023 . Genetically engineered mouse models of head and neck cancers . Oncogene , 42 ( 35 ): 2593 - 2609 . https://doi.org/10.1038/s41388-023-02783-7 https://doi.org/10.1038/s41388-023-02783-7

Tian JG , Cui XG , Feng YD , et al. , 2018 . Inhibition of WNT7A-β-catenin signaling pathway sensitizes oral squamous cell carcinoma to cisplatin . Int J Clin Exp Pathol , 11 ( 10 ): 4926 - 4933 .

Umar SA , Dong B , Nihal M , et al. , 2022 . Frizzled receptors in melanomagenesis: from molecular interactions to target identification . Front Oncol , 12 : 1096134 . https://doi.org/10.3389/fonc.2022.1096134 https://doi.org/10.3389/fonc.2022.1096134

Urzì O , Gasparro R , Costanzo E , et al. , 2023 . Three-dimensional cell cultures: the bridge between in vitro and in vivo models . Int J Mol Sci , 24 ( 15 ): 12046 . https://doi.org/10.3390/ijms241512046 https://doi.org/10.3390/ijms241512046

Vahle AK , Kerem A , Öztürk E , et al. , 2012 . Optimization of an orthotopic murine model of head and neck squamous cell carcinoma in fully immunocompetent mice ‒ role of toll-like-receptor 4 expressed on host cells . Cancer Lett , 317 ( 2 ): 199 - 206 . https://doi.org/10.1016/j.canlet.2011.11.027 https://doi.org/10.1016/j.canlet.2011.11.027

Verrelle P , Gestraud P , Poyer F , et al. , 2024 . Integrated high-throughput screening and large-scale isobolographic analysis to accelerate the discovery of radiosensitizers with greater selectivity for cancer cells . Int J Radiat Oncol Biol Phys , 118 ( 5 ): 1294 - 1307 . https://doi.org/10.1016/j.ijrobp.2023.09.044 https://doi.org/10.1016/j.ijrobp.2023.09.044

Vijayakumar G , Narwal A , Kamboj M , et al. , 2020 . Association of SOX2, OCT4 and WNT5A expression in oral epithelial dysplasia and oral squamous cell carcinoma: an immunohistochemical study . Head Neck Pathol , 14 ( 3 ): 749 - 757 . https://doi.org/10.1007/s12105-019-01114-1 https://doi.org/10.1007/s12105-019-01114-1

Walrath JC , Hawes JJ , van Dyke T , et al. , 2010 . Genetically engineered mouse models in cancer research . Adv Cancer Res , 106 : 113 - 164 . https://doi.org/10.1016/s0065-230x(10)06004-5 https://doi.org/10.1016/s0065-230x(10)06004-5

Wang YF , Cao Z , Liu FJ , et al. , 2021 . Clinical significance of activated Wnt/β-catenin signaling in apoptosis inhibition of oral cancer . Open Life Sci , 16 ( 1 ): 1045 - 1052 . https://doi.org/10.1515/biol-2021-0104 https://doi.org/10.1515/biol-2021-0104

Wang ZM , Luo JQ , Xu LY , et al. , 2018 . Harnessing low-density lipoprotein receptor protein 6 (LRP6) genetic variation and Wnt signaling for innovative diagnostics in complex diseases . Pharmacogenomics J , 18 ( 3 ): 351 - 358 . https://doi.org/10.1038/tpj.2017.28 https://doi.org/10.1038/tpj.2017.28

Wanigasekara J , Cullen PJ , Bourke P , et al. , 2023 . Advances in 3D culture systems for therapeutic discovery and development in brain cancer . Drug Discov Today , 28 ( 2 ): 103426 . https://doi.org/10.1016/j.drudis.2022.103426 https://doi.org/10.1016/j.drudis.2022.103426

Xie H , Ma YD , Li J , et al. , 2020 . WNT7A promotes EGF-induced migration of oral squamous cell carcinoma cells by activating β-catenin/MMP9-mediated signaling . Front Pharmacol , 11 : 98 . https://doi.org/10.3389/fphar.2020.00098 https://doi.org/10.3389/fphar.2020.00098

Xie J , Huang L , Lu YG , et al. , 2021 . Roles of the Wnt signaling pathway in head and neck squamous cell carcinoma . Front Mol Biosci , 7 : 590912 . https://doi.org/10.3389/fmolb.2020.590912 https://doi.org/10.3389/fmolb.2020.590912

Xu F , Peng LL , Feng JY , et al. , 2023 . A prediction model of nodal metastasis in cN0 oral squamous cell carcinoma using metabolic and pathological variables . Cancer Imaging , 23 : 34 . https://doi.org/10.1186/s40644-023-00552-z https://doi.org/10.1186/s40644-023-00552-z

Yang WB , Zhang SH , Li TL , et al. , 2023 . Single-cell analysis reveals that cancer-associated fibroblasts stimulate oral squamous cell carcinoma invasion via the TGF-β/Smad pathway . Acta Biochim Biophys Sin (Shanghai) , 55 ( 2 ): 262 - 273 . https://cstr.cn/32197.14.abbs.2022132 https://cstr.cn/32197.14.abbs.2022132

Yu FY , Yu CH , Li FF , et al. , 2021 . Wnt/β-catenin signaling in cancers and targeted therapies . Signal Transduct Target Ther , 6 : 307 . https://doi.org/10.1038/s41392-021-00701-5 https://doi.org/10.1038/s41392-021-00701-5

Yuan Y , Xie XY , Jiang YC , et al. , 2017 . LRP6 is identified as a potential prognostic marker for oral squamous cell carcinoma via MALDI-IMS . Cell Death Dis , 8 ( 9 ): e3035 . https://doi.org/10.1038/cddis.2017.433 https://doi.org/10.1038/cddis.2017.433

Zanella ER , Grassi E , Trusolino L , 2022 . Towards precision oncology with patient-derived xenografts . Nat Rev Clin Oncol , 19 ( 11 ): 719 - 732 . https://doi.org/10.1038/s41571-022-00682-6 https://doi.org/10.1038/s41571-022-00682-6

Zeng CM , Chen Z , Fu L , 2018 . Frizzled receptors as potential therapeutic targets in human cancers . Int J Mol Sci , 19 ( 5 ): 1543 . https://doi.org/10.3390/ijms19051543 https://doi.org/10.3390/ijms19051543

Zhang CP , Hao YL , Sun YY , et al. , 2019 . Quercetin suppresses the tumorigenesis of oral squamous cell carcinoma by regulating microRNA-22/WNT1/β-catenin axis . J Pharmacol Sci , 140 ( 2 ): 128 - 136 . https://doi.org/10.1016/j.jphs.2019.03.005 https://doi.org/10.1016/j.jphs.2019.03.005

Zhang EJ , Li ZN , Xu ZF , et al. , 2015 . Frizzled2 mediates the migration and invasion of human oral squamous cell carcinoma cells through the regulation of the signal transducer and activator of transcription-3 signaling pathway . Oncol Rep , 34 ( 6 ): 3061 - 3067 . https://doi.org/10.3892/or.2015.4285 https://doi.org/10.3892/or.2015.4285

Zhang Y , Liu SH , Qu DW , et al. , 2017 . Kif4A mediate the accumulation and reeducation of THP-1 derived macrophages via regulation of CCL2-CCR2 expression in crosstalking with OSCC . Sci Rep , 7 : 2226 . https://doi.org/10.1038/s41598-017-02261-7 https://doi.org/10.1038/s41598-017-02261-7

Zhang YH , Zhang YS , Niu WW , et al. , 2021 . Experimental study of almonertinib crossing the blood-brain barrier in EGFR-mutant NSCLC brain metastasis and spinal cord metastasis models . Front Pharmacol , 12 : 750031 . https://doi.org/10.3389/fphar.2021.750031 https://doi.org/10.3389/fphar.2021.750031

Zhang YL , Zu D , Chen Z , et al. , 2020 . An update on Wnt signaling pathway in cancer . Transl Cancer Res , 9 ( 2 ): 1246 - 1252 . https://doi.org/10.21037/tcr.2019.12.50 https://doi.org/10.21037/tcr.2019.12.50

Zhang YQ , Liu CX , Duan XL , et al. , 2014 . CREPT/RPRD1B, a recently identified novel protein highly expressed in tumors, enhances the β-catenin·TCF4 transcriptional activity in response to Wnt signaling . J Biol Chem , 289 ( 33 ): 22589 - 22599 . https://doi.org/10.1074/jbc.M114.560979 https://doi.org/10.1074/jbc.M114.560979

Zhao BR , Qin X , Fu R , et al. , 2024 . Supramolecular nanodrug targeting CDK4/6 overcomes BAG1 mediated cisplatin resistance in oral squamous cell carcinoma . J Control Release , 368 : 623 - 636 . https://doi.org/10.1016/j.jconrel.2024.03.014 https://doi.org/10.1016/j.jconrel.2024.03.014

Zhong L , Liu YT , Wang K , et al. , 2018 . Biomarkers: paving stones on the road towards the personalized precision medicine for oral squamous cell carcinoma . BMC Cancer , 18 : 911 . https://doi.org/10.1186/s12885-018-4806-7 https://doi.org/10.1186/s12885-018-4806-7

Zhu EX , Li XM , Zhu L , et al. , 2005 . Expression of Wnt5a and β-catenin in Chinese oral squamous cell carcinoma of tongue . J Hard Tissue Biol , 14 ( 2 ): 247 - 248 . https://doi.org/10.2485/jhtb.14.247 https://doi.org/10.2485/jhtb.14.247

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