A proliferative to invasive switch is mediated by srGAP1 downregulation through the activation of TGF-β2 signaling.

ABSTRACT: Many breast cancer (BC) patients suffer from complications of metastatic disease. To form metastases, cancer cells must become migratory and coordinate both invasive and proliferative programs at distant organs. Here, we identify srGAP1 as a regulator of a proliferative-to-invasive switch in BC cells. High-resolution light-sheet microscopy demonstrates that BC cells can form actin-rich protrusions during extravasation. srGAP1^low cells display a motile and invasive phenotype that facilitates their extravasation from blood vessels, as shown in zebrafish and mouse models, while attenuating tumor growth. Interestingly, a population of srGAP1^low cells remain as solitary disseminated tumor cells in the lungs of mice bearing BC tumors. Overall, srGAP1^low cells hav

SUBMITTER: Mondal C 

PROVIDER: S-EPMC9596226 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature