Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

ITGB1/FERMT1 mechanoactivation enhances CD44 characteristic stemness in oral squamous cell carcinoma via ubiquitin-dependent CK1α degradation

Oncogene volume 44, pages 1530–1544 (2025)Cite this article

Subjects

Abstract

Cancer stem cells (CSCs) contribute to chemotherapy resistance and poor prognosis, posing significant challenges in the treatment of oral squamous cell carcinoma. The extracellular matrix (ECM)-constructed microenvironment remodels the niche of CSCs. Yet mechanisms by which biophysical properties of ECM relate to CSCs remain undefined. Here, our findings link ECM mechanical stimuli to CSCs phenotype transition, and propose that ECM stiffening mechanoactivates tumor cells to dedifferentiate and acquire CD44+ stem cell-like characteristics through noncanonical mechanotransduction. ITGB1 senses and transduces biomechanical signals, while FERMT1 acts as an intracellular mechanotransduction downstream, activating CSCs. Mechanistically, FERMT1 promotes the proteasomal degradation of CK1α by E3 ubiquitin ligase MIB1, thereby triggering Wnt signaling pathway. Combining targeted ECM softening with mechanotransduction inhibition strategy significantly attenuates tumor stemness and chemoresistance in vivo. Therefore, our findings highlight the role of ECM in regulating CSCs via biomechanical-dependent manner, suggesting the ECM/ITGB1/FERMT1/Wnt axis as a promising therapeutic target for CSCs therapy.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Matrix stiffening mediates the enhancement of CSCs properties in OSCC.
Fig. 2: Biophysical properties of ECM direct the phenotype transition of CSCs characterized by CD44.
Fig. 3: ITGB1 regulates CSCs phenotype in a matrix-dependent manner.
Fig. 4: ITGB1/FERMT1 axis triggered by ECM stiffening activates Wnt/β-catenin signaling pathway.
Fig. 5: FERMT1 promotes ubiquitin-dependent CK1α degradation by MIB1.
Fig. 6: Targeted ECM softening combined with mechanotransduction inhibition strategy attenuates tumor stemness and chemoresistance in PDOX models.
Fig. 7: Schematic diagram of the mechanisms by which ECM remodeling regulates CSCs properties of OSCC.

Similar content being viewed by others

Data availability

The datasets generated during the current study are available from the corresponding author upon reasonable request.

References

  1. Koren E, Fuchs Y. The bad seed: Cancer stem cells in tumor development and resistance. Drug Resistance Updates. 2016;28:1–12.

    Article  PubMed  Google Scholar 

  2. Wang C, Li Y, Jia L, Kim JK, Li J, Deng P, et al. CD276 expression enables squamous cell carcinoma stem cells to evade immune surveillance. Cell Stem Cell. 2021;28:1597–1613.e7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Chen D, Wu M, Li Y, Chang I, Yuan Q, Ekimyan-Salvo M, et al. Targeting BMI1+ Cancer Stem Cells Overcomes Chemoresistance and Inhibits Metastases in Squamous Cell Carcinoma. Cell Stem Cell. 2017;20:621–634.e6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Li J, Stanger BZ. How tumor cell dedifferentiation drives immune evasion and resistance to immunotherapy. Cancer Res. 2020;80:4037–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Driessens G, Beck B, Caauwe A, Simons BD, Blanpain C. Defining the mode of tumour growth by clonal analysis. Nature. 2012;488:527–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Zhang J, Li L. Stem cell niche: microenvironment and beyond. J Biol Chem. 2008;283:9499–503.

    Article  CAS  PubMed  Google Scholar 

  7. Zhao H, Li R, Chen Y, Yang X, Shang Z. Stromal nicotinamide N-methyltransferase orchestrates the crosstalk between fibroblasts and tumour cells in oral squamous cell carcinoma: evidence from patient-derived assembled organoids. Oncogene. 2023;42:1166–80.

    Article  CAS  PubMed  Google Scholar 

  8. Zhao H, Yan C, Hu Y, Mu L, Liu S, Huang K, et al. Differentiated cancer cell-originated lactate promotes the self-renewal of cancer stem cells in patient-derived colorectal cancer organoids. Cancer Lett. 2020;493:236–44.

    Article  CAS  PubMed  Google Scholar 

  9. Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med. 2013;19:1423–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sahai E, Astsaturov I, Cukierman E, DeNardo DG, Egeblad M, Evans RM, et al. A framework for advancing our understanding of cancer-associated fibroblasts. Nat Rev Cancer. 2020;20:174–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Cox TR. The matrix in cancer. Nat Rev Cancer. 2021;21:217–38.

    Article  CAS  PubMed  Google Scholar 

  12. Kai F, Laklai H, Weaver VM. Force Matters: Biomechanical Regulation of Cell Invasion and Migration in Disease. Trends Cell Biol. 2016;26:486–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Liu X, Ye Y, Zhu L, Xiao X, Zhou B, Gu Y, et al. Niche stiffness sustains cancer stemness via TAZ and NANOG phase separation. Nat Commun. 2023;14:238.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Yang N, Chen T, Wang L, Liu R, Niu Y, Sun L, et al. CXCR4 mediates matrix stiffness-induced downregulation of UBTD1 driving hepatocellular carcinoma progression via YAP signaling pathway. Theranostics. 2020;10:5790–801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ng K-Y, Shea QT, Wong T-L, Luk ST, Tong M, Lo C-M, et al. Chemotherapy-Enriched THBS2-Deficient Cancer Stem Cells Drive Hepatocarcinogenesis through Matrix Softness Induced Histone H3 Modifications. Adv Sci. 2021;8:2002483.

    Article  CAS  Google Scholar 

  16. Zhang M, Xu C, Wang H, Peng Y, Li H, Zhou Y, et al. Soft fibrin matrix downregulates DAB2IP to promote Nanog-dependent growth of colon tumor-repopulating cells. Cell Death Dis. 2019;10:151.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Liu J, Tan Y, Zhang H, Zhang Y, Xu P, Chen J, et al. Soft fibrin gels promote selection and growth of tumorigenic cells. Nat Mater. 2012;11:734–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Northey JJ, Przybyla L, Weaver VM. Tissue Force Programs Cell Fate and Tumor Aggression. Cancer Discov. 2017;7:1224–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ross TD, Coon BG, Yun S, Baeyens N, Tanaka K, Ouyang M, et al. Integrins in mechanotransduction. Curr Opin Cell Biol. 2013;25:613–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Fu H-L, Valiathan RR, Arkwright R, Sohail A, Mihai C, Kumarasiri M, et al. Discoidin Domain Receptors: Unique Receptor Tyrosine Kinases in Collagen-mediated Signaling. J Biol Chem. 2013;288:7430–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Paszek MJ, Weaver VM. The Tension Mounts: Mechanics Meets Morphogenesis and Malignancy. J Mammary Gland Biol Neoplasia. 2004;9:325–42.

    Article  PubMed  Google Scholar 

  22. Douguet D, Honoré E. Mammalian Mechanoelectrical Transduction: Structure and Function of Force-Gated Ion Channels. Cell. 2019;179:340–54.

    Article  CAS  PubMed  Google Scholar 

  23. Delmas P, Coste B. Mechano-Gated Ion Channels in Sensory Systems. Cell. 2013;155:278–84.

    Article  CAS  PubMed  Google Scholar 

  24. Murthy SE, Dubin AE, Patapoutian A. Piezos thrive under pressure: mechanically activated ion channels in health and disease. Nat Rev Mol Cell Biol. 2017;18:771–83.

    Article  CAS  PubMed  Google Scholar 

  25. Grasset EM, Bertero T, Bozec A, Friard J, Bourget I, Pisano S, et al. Matrix stiffening and EGFR cooperate to promote the collective invasion of cancer cells. Cancer Res. 2018;78:5229–42.

    Article  CAS  PubMed  Google Scholar 

  26. Han T, Jiang Y, Wang X, Deng S, Hu Y, Jin Q, et al. 3D matrix promotes cell dedifferentiation into colorectal cancer stem cells via integrin/cytoskeleton/glycolysis signaling. Cancer Sci. 2022;113:3826–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Haake SM, Plosa EJ, Kropski JA, Venton LA, Reddy A, Bock F, et al. Ligand-independent integrin 1 signaling supports lung adenocarcinoma development. JCI Insight. 2022;7:e154098.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Gjorevski N, Sachs N, Manfrin A, Giger S, Bragina ME, Ordóñez-Morán P, et al. Designer matrices for intestinal stem cell and organoid culture. Nature. 2016;539:560–4.

    Article  CAS  PubMed  Google Scholar 

  29. Lv H, Li L, Sun M, Zhang Y, Chen L, Rong Y, et al. Mechanism of regulation of stem cell differentiation by matrix stiffness. Stem Cell Res Ther. 2015;6:103.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Bertero T, Oldham WM, Grasset EM, Bourget I, Boulter E, Pisano S, et al. Tumor-stroma mechanics coordinate amino acid availability to sustain tumor growth and malignancy. Cell Metab. 2019;29:124–40.

    Article  CAS  PubMed  Google Scholar 

  31. Kechagia JZ, Ivaska J, Roca-Cusachs P. Integrins as biomechanical sensors of the microenvironment. Nat Rev Mol Cell Biol. 2019;20:457–73.

    Article  CAS  PubMed  Google Scholar 

  32. Kim J-H, Park S-Y, Jun Y, Kim J-Y, Nam J-S. Roles of Wnt Target Genes in the Journey of Cancer Stem Cells. Int J Mol Sci. 2017;18:1604.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Fodde R, Brabletz T. Wnt/β-catenin signaling in cancer stemness and malignant behavior. Curr Opin Cell Biol. 2007;19:150–8.

    Article  CAS  PubMed  Google Scholar 

  34. Pohl C, Dikic I. Cellular quality control by the ubiquitin-proteasome system and autophagy. Science. 2019;366:818–22.

    Article  CAS  PubMed  Google Scholar 

  35. Kim E, Choi S, Kang B, Kong J, Kim Y, Yoon WH, et al. Creation of bladder assembloids mimicking tissue regeneration and cancer. Nature. 2020;588:664–9.

    Article  CAS  PubMed  Google Scholar 

  36. Batlle E, Clevers H. Cancer stem cells revisited. Nat Med. 2017;23:1124–34.

    Article  CAS  PubMed  Google Scholar 

  37. Zhao Y, Dong Q, Li J, Zhang K, Qin J, Zhao J, et al. Targeting cancer stem cells and their niche: perspectives for future therapeutic targets and strategies. Semin Cancer Biol. 2018;53:139–55.

    Article  CAS  PubMed  Google Scholar 

  38. Chen Y, Zhao H, Liang W, Jiang E, Zhou X, Shao Z, et al. Autophagy regulates the cancer stem cell phenotype of head and neck squamous cell carcinoma through the noncanonical FOXO3/SOX2 axis. Oncogene. 2022;41:634–46.

    Article  CAS  PubMed  Google Scholar 

  39. Xiao Y, Yu D. Tumor microenvironment as a therapeutic target in cancer. Pharmacol Therapeutics. 2021;221:107753.

    Article  CAS  Google Scholar 

  40. Engler AJ, Sen S, Sweeney HL, Discher DE. Matrix Elasticity Directs Stem Cell Lineage Specification. Cell. 2006;126:677–89.

    Article  CAS  PubMed  Google Scholar 

  41. Butcher DT, Alliston T, Weaver VM. A tense situation: forcing tumour progression. Nat Rev Cancer. 2009;9:108–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Pang M-F, Siedlik MJ, Han S, Stallings-Mann M, Radisky DC, Nelson CM. Tissue Stiffness and Hypoxia Modulate the Integrin-Linked Kinase ILK to Control Breast Cancer Stem-like Cells. Cancer Res. 2016;76:5277–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Wong SY, Ulrich TA, Deleyrolle LP, MacKay JL, Lin J-MG, Martuscello RT, et al. Constitutive Activation of Myosin-Dependent Contractility Sensitizes Glioma Tumor-Initiating Cells to Mechanical Inputs and Reduces Tissue Invasion. Cancer Res. 2015;75:1113–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Dvorak HF. Tumors: Wounds That Do Not Heal—Redux. Cancer Immunol Res. 2015;3:1–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Massagué J. TGFβ in Cancer. Cell. 2008;134:215–30.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001;357:539–45.

    Article  CAS  PubMed  Google Scholar 

  47. Mancini A, Gentile MT, Pentimalli F, Cortellino S, Grieco M, Giordano A. Multiple aspects of matrix stiffness in cancer progression. Front Oncol. 2024;2:1406644.

    Article  Google Scholar 

  48. Panciera T, Citron A, Di Biagio D, Battilana G, Gandin A, Giulitti S, et al. Reprogramming normal cells into tumour precursors requires ECM stiffness and oncogene-mediated changes of cell mechanical properties. Nat Mater. 2020;19:797–806.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Wei SC, Fattet L, Tsai JH, Guo Y, Pai VH, Majeski HE, et al. Matrix stiffness drives epithelial–mesenchymal transition and tumour metastasis through a TWIST1–G3BP2 mechanotransduction pathway. Nat Cell Biol. 2015;17:678–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Liu T, Babaniyi OA, Hall TJ, Barbone PE, Oberai AA. Noninvasive In-Vivo Quantification of Mechanical Heterogeneity of Invasive Breast Carcinomas. PLOS ONE. 2015;10:e0130258.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Sun Y, Li H, Chen Q, Luo Q, Song G. The distribution of liver cancer stem cells correlates with the mechanical heterogeneity of liver cancer tissue. Histochem Cell Biol. 2021;156:47–58.

    Article  CAS  PubMed  Google Scholar 

  52. Tung JC, Barnes JM, Desai SR, Sistrunk C, Conklin MW, Schedin P, et al. Tumor mechanics and metabolic dysfunction. Free Radic Biol Med. 2015;79:269–80.

    Article  CAS  PubMed  Google Scholar 

  53. Hamidi H, Ivaska J. Every step of the way: integrins in cancer progression and metastasis. Nat Rev Cancer. 2018;18:533–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Ünlü B, Kocatürk B, Rondon AMR, Lewis CS, Swier N, van den Akker RFP, et al. Integrin regulation by tissue factor promotes cancer stemness and metastatic dissemination in breast cancer. Oncogene. 2022;41:5176–85.

    Article  PubMed  Google Scholar 

  55. Stupp R, Hegi ME, Gorlia T, Erridge SC, Perry J, Hong Y-K, et al. Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15:1100–8.

    Article  CAS  PubMed  Google Scholar 

  56. Elez E, Kocáková I, Höhler T, Martens U, Bokemeyer C, Cutsem EV, et al. Abituzumab Combined with Cetuximab Plus Irinotecan Versus Cetuximab Plus Irinotecan Alone, as Second-Line Treatment for Patients with KRAS Wild-Type Metastatic Colorectal Cancer: The Poseidon Phase I/Randomized Phase II Trial. Ann Oncol. 2014;25:ii107.

    Article  Google Scholar 

  57. Larjava H, Plow EF, Wu C. Kindlins: essential regulators of integrin signalling and cell–matrix adhesion. EMBO Rep. 2008;9:1203–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Kloeker S, Major MB, Calderwood DA, Ginsberg MH, Jones DA, Beckerle MC. The Kindler syndrome protein is regulated by transforming growth factor-β and involved in integrin-mediated adhesion. J Biol Chem. 2004;279:6824–33.

    Article  CAS  PubMed  Google Scholar 

  59. Liu C-C, Cai D-L, Sun F, Wu Z-H, Yue B, Zhao S-L, et al. FERMT1 mediates epithelial–mesenchymal transition to promote colon cancer metastasis via modulation of β-catenin transcriptional activity. Oncogene. 2017;36:1779–92.

    Article  CAS  PubMed  Google Scholar 

  60. Yue B, Liu C, Sun H, Liu M, Song C, Cui R, et al. A positive feed-forward loop between LncRNA-CYTOR and Wnt/β-catenin signaling promotes metastasis of colon cancer. Mol Ther. 2018;26:1287–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Samuel MS, Lopez JI, McGhee EJ, Croft DR, Strachan D, Timpson P, et al. Actomyosin-Mediated Cellular Tension Drives Increased Tissue Stiffness and β-Catenin Activation to Induce Epidermal Hyperplasia and Tumor Growth. Cancer Cell. 2024;42:317.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Park JS, Burckhardt CJ, Lazcano R, Solis LM, Isogai T, Li L, et al. Mechanical regulation of glycolysis via cytoskeleton architecture. Nature. 2020;578:621–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Cui L, Lu Y, Zheng J, Guo B, Zhao X. ACTN1 promotes HNSCC tumorigenesis and cisplatin resistance by enhancing MYH9-dependent degradation of GSK-3β and integrin β1-mediated phosphorylation of FAK. J Exp Clin Cancer Res. 2023;42:335.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Piersma B, Hayward M-K, Weaver VM. Fibrosis and cancer: A strained relationship. Biochim Biophys Acta Rev Cancer. 2020;1873:188356.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Levental KR, Yu H, Kass L, Lakins JN, Egeblad M, Erler JT, et al. Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling. Cell. 2009;139:891–906.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Palamakumbura AH, Vora SR, Nugent MA, Kirsch KH, Sonenshein GE, Trackman PC. Lysyl oxidase propeptide inhibits prostate cancer cell growth by mechanisms that target FGF-2-cell binding and signaling. Oncogene. 2009;28:3390–3400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Salmon H, Franciszkiewicz K, Damotte D, Dieu-Nosjean M-C, Validire P, Trautmann A, et al. Matrix architecture defines the preferential localization and migration of T cells into the stroma of human lung tumors. J Clin Invest. 2012;122:899–910.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Kuczek DE, Larsen AMH, Thorseth M-L, Carretta M, Kalvisa A, Siersbæk MS, et al. Collagen density regulates the activity of tumor-infiltrating T cells. J Immunother Cancer. 2019;7:68.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Nicolas-Boluda A, Vaquero J, Vimeux L, Guilbert T, Barrin S, Kantari-Mimoun C, et al. Tumor stiffening reversion through collagen crosslinking inhibition improves T cell migration and anti-PD-1 treatment. eLife. 2021;10:e58688.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Di Martino JS, Nobre AR, Mondal C, Taha I, Farias EF, Fertig EJ, et al. A tumor-derived type III collagen-rich ECM niche regulates tumor cell dormancy. Nat Cancer. 2022;3:90–107.

    Article  PubMed  Google Scholar 

  71. Mittelheisser V, Gensbittel V, Bonati L, Li W, Tang L, Goetz JG. Evidence and therapeutic implications of biomechanically regulated immunosurveillance in cancer and other diseases. Nat Nanotechnol. 2024;19:281–97.

    Article  CAS  PubMed  Google Scholar 

  72. Li X, Jiang E, Zhao H, Chen Y, Xu Y, Feng C, et al. Glycometabolic reprogramming-mediated proangiogenic phenotype enhancement of cancer-associated fibroblasts in oral squamous cell carcinoma: role of PGC-1α/PFKFB3 axis. Br J Cancer. 2022;127:449–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Zhao H, Jiang E, Shang Z. 3D Co-culture of Cancer-Associated Fibroblast with Oral Cancer Organoids. J Dent Res. 2021;100:201–8.

    Article  CAS  PubMed  Google Scholar 

  74. Bao M, Chen Y, Liu J-T, Bao H, Wang W-B, Qi Y-X, et al. Extracellular matrix stiffness controls VEGF165 secretion and neuroblastoma angiogenesis via the YAP/RUNX2/SRSF1 axis. Angiogenesis. 2022;25:71–86.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors are grateful to Junjie Zhang (Frontier Science Center for Immunology and Metabolism, Wuhan University) for his support and help.

Funding

This study was supported by National Key R&D Programme of China (Grant No. 2022YFC2504200 to Z. Shang) and National Natural Science Foundation of China (Grant No. 82273306).

Author information

Authors and Affiliations

  1. State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China

    Xiang Li, Hui Zhao, Erhui Jiang, Pan Liu, Yang Chen, Yue Wang, Ji Li, Yufei Wu, Zhenan Liu & Zhengjun Shang

  2. Department of Oral and Maxillofacial-Head and Neck Oncology, School of Stomatology–Hospital of Stomatology, Wuhan University, Wuhan, China

    Hui Zhao, Erhui Jiang & Zhengjun Shang

  3. Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wuhan University, Wuhan, China

    Yang Chen

Authors
  1. Xiang Li
    View author publications

    Search author on:PubMed Google Scholar

  2. Hui Zhao
    View author publications

    Search author on:PubMed Google Scholar

  3. Erhui Jiang
    View author publications

    Search author on:PubMed Google Scholar

  4. Pan Liu
    View author publications

    Search author on:PubMed Google Scholar

  5. Yang Chen
    View author publications

    Search author on:PubMed Google Scholar

  6. Yue Wang
    View author publications

    Search author on:PubMed Google Scholar

  7. Ji Li
    View author publications

    Search author on:PubMed Google Scholar

  8. Yufei Wu
    View author publications

    Search author on:PubMed Google Scholar

  9. Zhenan Liu
    View author publications

    Search author on:PubMed Google Scholar

  10. Zhengjun Shang
    View author publications

    Search author on:PubMed Google Scholar

Contributions

The authors contributed in the following way: designed and performed the research: XL; wrote the manuscripts: XL; data analysis: EJ and YC; performed experiments: PL, YW, JL, YW and ZL; supervised the research: ZS and HZ.

Corresponding author

Correspondence to Zhengjun Shang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

This study was approved and supervised by the Ethics Committee of the School and Hospital of Stomatology, Wuhan University (2022LUNSHENZIA05), and was performed in accordance with the relevant guidelines and regulations. All experiments involving patients were conducted with their informed consent. All animal studies were conducted following the guidance of the Ethical Committee on Animal Experiments of Animal Care Committee of Wuhan University (S07924020H). This research did not involve identifiable images of human participants.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, X., Zhao, H., Jiang, E. et al. ITGB1/FERMT1 mechanoactivation enhances CD44 characteristic stemness in oral squamous cell carcinoma via ubiquitin-dependent CK1α degradation. Oncogene 44, 1530–1544 (2025). https://doi.org/10.1038/s41388-025-03317-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41388-025-03317-z

This article is cited by

Search

Advanced search

Quick links