CBX7 Promotes Lung Adenocarcinoma Metastasis by Transcriptionally Repressing SOCS3

In lung adenocarcinoma (LUAD), metastasis is a leading cause of mortality and notably tends to occur at an early stage of the disease. CBX7, a component of canonical Polycomb Repressive Complex 1 (PRC1) which mediates transcriptional repression, exhibits complex and context-dependent functions across different types of cancer. However, the roles of CBX7 in LUAD metastasis remain largely uncharacterized. Here we report that overexpression of CBX7 promotes, whereas its knockdown suppresses, LUAD cell migration and invasion in vitro. In vivo studies further confirm the pro-metastatic role of CBX7 in LUAD. Mechanistically, CBX7 suppresses the expression of SOCS3, which has been reported to be involved in cancer cell migration and invasion. At the molecular level, CBX7 binds to SOCS3 transcription start site (TSS) downstream region to establish monoubiquitination of histone H2A at lysine 119 (H2AK119ub), leading to transcriptional repression of SOCS3. Furthermore, knockdown of SOCS3 rescues the reduced migration and invasion caused by CBX7 depletion in LUAD cells. Together, our findings identify CBX7 as a positive regulator of LUAD metastasis and suggest its potential as a therapeutic target for LUAD treatment. Examination of gene expression changes in control and CBX7 overexpression A549 cells