TGFβ signaling sensitizes MEKi-resistant human melanoma to targeted therapy-induced apoptosis.

ABSTRACT: The TGFβ signaling pathway is known for its pleiotropic functions in a plethora of biological processes. In melanoma, TGFβ signaling promotes invasiveness and metastasis formation. However, its involvement in the response to therapy is controversial. While several studies have linked TGFβ signaling to elevated resistance to targeted therapy in melanoma, separate findings have indicated a favorable treatment response through TGFβ-mediated increase of cell death. We now found that the outcome of TGFβ signaling in the context of targeted therapy is dose dependent. Unlike low doses, high levels of TGFβ signal activation induce apoptosis upon simultaneous MAPK pathway inhibition, even in targeted therapy resistant melanoma cell lines. Using transcriptomic analyses, combined with genomic target

SUBMITTER: Loos B 

PROVIDER: S-EPMC11663225 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature