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Updated: Feb 28, 2026

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Oncogenic K-Ras upregulates ITGA6 expression via FOSL1 to induce anoikis resistance and synergizes with αV-Class

K Zhang1, S-M Myllymäki1, P Gao1

  • 1Biocenter Oulu, Centre of Excellence in Cell-Extracellular Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.

Oncogene
|June 13, 2017
PubMed

Insights

Oncogenic K-RasV12 boosts cancer cell invasion by upregulating α6-integrin and downregulating αV-integrin. This crosstalk impacts tumorigenesis and metastasis, offering new therapeutic targets for K-RasV12-driven cancers.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Integrin-mediated signaling is crucial for cancer cell proliferation, survival, and invasion.
  • The interplay between integrins and oncogenes in tumorigenesis and metastasis remains incompletely understood.

Purpose of the Study:

  • To elucidate the signaling pathways linking oncogenic K-RasV12 to integrin function in cancer.
  • To investigate the roles of α6- and αV-integrins in K-RasV12-driven tumorigenesis and metastasis.

Main Methods:

  • Utilized Madin-Darby canine kidney (MDCK) cells expressing oncogenic K-RasV12.
  • Investigated signaling cascades including mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK)/Fos-related antigen 1.
  • Performed transcriptomic analysis and re-expression studies of integrins.

Main Results:

  • Oncogenic K-RasV12 upregulates α6-integrin via the ERK/Fra-1 pathway, enhancing metastatic capacity and anoikis resistance.
  • K-RasV12 transformation leads to downregulation of αV-integrins.
  • Re-expression of αV-integrin induces epithelial-mesenchymal transition (EMT), increasing cell motility and invasion.

Conclusions:

  • Delineated signaling cascades connecting K-RasV12 with α6- and αV-integrin functions in cancer.
  • Highlighted the critical roles of α6- and αV-integrins in modulating cancer cell survival and tumorigenesis.
  • Identified potential therapeutic strategies targeting K-RasV12 mutants through integrin modulation.

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