In vitro kinase assays Identified of STAT1 phosphorylation sites-mediated LATS2

ABSTRACT: LATS1/2 are frequently down-regulated or mutated in endometrial cancer (EC), yet their exact role in endometrial tumor progression remains unclear. In this study, we unexpectedly discovered a new function of LATS1/2 in regulating MHC class I expression in EC. Knockout of LATS1/2 in EC cells led to significant down-regulation of multiple genes within the MHC/HLA Class I family, which weakened the killing effects of PBMCs on tumor cells. Importantly, we found that the regulation of MHC/HLA expression by LATS1/2 does not depend on the classical Hippo pathway but rather involves their direct interaction with STAT1. This interaction causes STAT1 to be phosphorylated at Ser727 or Ser532, promoting its accumulation and movement into the nucleus and enhancing the transcriptional activation of IRF1/NLRC5 on MHC-I. Additionally, we demonstrated that the kinase-dead mutant LATS1/2 weakens STAT1 phosphorylation at Ser727, supporting our findings. Our results show a positive correlation between the expression levels of LATS1/2, MHC-I, CD8, and p-STAT1 in tissue samples of EC, providing further evidence to support our discoveries. Overall, our findings reveal novel molecular mechanisms underlying tumor immunogenicity deficiency and suggest that LATS1/2 may serve as an immunotherapy biomarker for targeting EC.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

SUBMITTER: Huiru Sun  

LAB HEAD: Qianlan Yang

PROVIDER: PXD043500 | Pride | 2024-06-16

REPOSITORIES: Pride