RhoA activation promotes glucose uptake to elevate proliferation in MAPK inhibitor resistant melanoma cells.

ABSTRACT: Cutaneous melanomas harboring a B-Raf^V600E mutation are treated with immune check point inhibitors or kinase inhibitor combination therapies relying on MAPK inhibitors (MAPKi) Dabrafenib and Trametinib (Curti and Faries, 2021). However, cells become resistant to treatments over the timespan of a few months. Resistance to MAPKi has been associated with adoption of an aggressive amoeboid phenotype characterized by elevated RhoA signaling, enhanced contractility and thick cortical filamentous actin (F-actin) structures (Kim et al., 2016; Misek et al., 2020). Targeting active RhoA through Rho-kinase (ROCK) inhibitors, either alone or in combination with immunotherapies, reverts MAPKi-resistance (Misek et al., 2020; Orgaz et al., 2020). Yet, the mechanisms for this behavior remain la

SUBMITTER: Murali VS 

PROVIDER: S-EPMC10802590 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature