Elevated Transglutaminase-2 in SOX10-Deficient Melanoma Promotes Tumor Onset and Decreases Intratumoral CD4+ T Cells.

ABSTRACT: Melanoma heterogeneity contributes to therapy resistance and immune evasion. The loss of SOX10, a neural crest lineage-specific transcription factor, leads to phenotypic switching from a proliferative cell state to an invasive, drug-tolerant cell state. SOX10-deficient cells are able to persist during immunotherapy treatment, highlighting the need to characterize the factors that regulate immune evasion downstream of SOX10 loss. Here, we found that SOX10-deficient melanoma cell lines and patient samples express elevated levels of TGM2, a transglutaminase family member. TGM2 upregulation in SOX10 knockout cells was reversed by inhibition of epigenetic reader BET proteins. Knockdown of TGM2 did not affect the SOX10-deficient invasive cell state; however, overexpression of TGM2 in syngeneic m

SUBMITTER: Caksa S 

PROVIDER: S-EPMC12398951 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature