The autophagy-independent role of BECN1 in colorectal cancer metastasis through regulating STAT3 signaling pathway activation.
2020
BECN1 is a critical regulator of autophagy, which plays important roles in tumor formation and metastasis. However, the autophagy-independent role of BECN1 and the clinical prediction value of BECN1 still need to be explored. Here, we observed significantly lower expression of BECN1 in colorectal cancers (CRCs) compared with adjacent normal colon tissue, and downregulation of BECN1 was positively related to poor prognosis in CRC patients. In addition, we found that knockdown of BECN1 markedly promoted CRC cell motility and invasion. Bioinformatics gene set enrichment analysis (GSEA) revealed that low levels of BECN1 were significantly correlated with the STAT3 signaling pathway in CRC. Consistently, knockdown of BECN1 increased the phosphorylation of STAT3 and activated the STAT3 signaling pathway in CRC cells. Furthermore, we demonstrated that STAT3 was involved in the CRC metastasis mediated by knockdown of BECN1 in vitro and in vivo. Mechanistically, knockdown of BECN1 promoted the phosphorylation of STAT3 via regulation of the interaction between STAT and JAK2 but did not inhibit autophagy. Our study revealed that BECN1 served as a negative regulator of CRC metastasis by regulating STAT3 signaling pathway activation in an autophagy-independent manner. The BECN1/JAK2/STAT3 signaling pathway can be used as a potential therapeutic target for metastatic CRC.
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