Data from Glioblastomas Require Integrin αvβ3/PAK4 Signaling to Escape Senescence
Year: 2023
Type: other
Abstract: Integrin αvβ3 has been implicated as a driver of aggressive and metastatic disease, and is upregulated during glioblastoma progression. Here, we demonstrate that integrin αvβ3 allows glioblastoma cells to counteract senescence through a novel tissue-specific effector mechanism involving recruitment and activation of the cytoskeletal regulatory kinase PAK4. Mechanistically, targeting either αvβ3 or PAK4 led to emergence of a p21-dependent, p53-independent cell senescence phenotype. Notably, glioblastoma cells did not exhibit a similar requirement for either other integrins or additional PAK family members. Moreover, αvβ3/PAK4 dependence was not found to be critical in epithelial cancers. Taken together, our findings established that glioblastomas are selectively addicted to this pathway as a strategy to evade oncogene-induced senescence, with implications that inhibiting the αvβ3–PAK4 signaling axis may offer novel therapeutic opportunities to target this aggressive cancer. Cancer Res; 75(21); 4466–73. ©2015 AACR.
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4392680444