Reduction in integrin a3b1 modulates lung cancer motility and invasion through p70S6K-dependent E-cadherin localization

Cell Mol Biol (Noisy-le-grand). 2024 Nov 27;70(11):115-121. doi: 10.14715/cmb/2024.70.11.17.

Abstract

In the current study, we investigated the effects and action mechanism of integrin a3b1 in modulating non-small cell lung cancer (NSCLC) growth and progression. Reduced expression of integrin a3 by RNA silencing in p53 wild-type A549 NSCLC cells inhibits cell migration and invasion, compared with those in control cells. These anti-migratory and anti-invasive properties in integrin a3-silenced cells were associated with epithelial cadherin (E-cadherin) distribution at cell-cell contacts, and these effects require the activation of p70 S6 kinase (p70S6K) as evidenced by treatment with rapamycin. Disruption of E-cadherin or blockade of p70S6K activation abrogated the ability of integrin a3-silencing to inhibit cell migration and invasion. In contrast, enhanced proliferation in integrin a3-silenced cells was not affected by the changes in E-cadherin expression. These findings demonstrate the ability of integrin a3b1 to differentially regulate NSCLC cell growth and progression depending on the p53 status, and suggest that integrin a3b1-p70S6K-p53 network may be a promising target for the treatment of NSCLC.

MeSH terms

  • A549 Cells
  • Cadherins* / genetics
  • Cadherins* / metabolism
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Cell Line, Tumor
  • Cell Movement* / genetics
  • Cell Proliferation*
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Neoplasm Invasiveness
  • RNA Interference
  • Ribosomal Protein S6 Kinases, 70-kDa* / genetics
  • Ribosomal Protein S6 Kinases, 70-kDa* / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Cadherins
  • Ribosomal Protein S6 Kinases, 70-kDa
  • Tumor Suppressor Protein p53