SRC-RAC1 signaling drives drug resistance to BRAF inhibition in de-differentiated cutaneous melanomas.

ABSTRACT: Rare gain-of-function mutations in RAC1 drive drug resistance to targeted BRAF inhibition in cutaneous melanoma. Here, we show that wildtype RAC1 is a critical driver of growth and drug resistance, but only in a subset of melanomas with elevated markers of de-differentiation. Similarly, SRC inhibition also selectively sensitized de-differentiated melanomas to BRAF inhibition. One possible mechanism may be the suppression of the de-differentiated state, as SRC and RAC1 maintained markers of de-differentiation in human melanoma cells. The functional differences between melanoma subtypes suggest that the clinical management of cutaneous melanoma can be enhanced by the knowledge of differentiation status. To simplify the task of classification, we developed a binary classification strategy bas

SUBMITTER: Zhu EY 

PROVIDER: S-EPMC9587254 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature