Cell Death Dis: The Role and Potential Mechanism of BECN1 in Colorectal Cancer Metastay

Cell autophagy is a life-promoting response involving the capture, degradation and recovery of intracellular proteins and organelles in lysosomesThe enhancement of cell autophagy in cancer can promote the survival of cancer cells in tumor microenvironment and promote the growth and invasion of cancer cellsBECN1 is a key regulatory factor for autophagy and plays an important role in tumor formation and metastasisThe BECN1 protein contains BH3 (Bcl-2 homologous) domain, CCD (curling helix) domain, and ECD (evolutionary conservative) domain, which can interact with Vps34 and other factors to regulate the formation of autophagy miniaserHowever, beCN1's non-dependent autophagy effect and its clinically predicted value remain to be studiedthe study found that BECN1 expression levels in colorectal cancer (CRC) were significantly lower than in neighboring normal colon tissue, and that lower levels of BECN1 expression were positively correlated with adverse prognosis in CRC patientsIn addition, the expression of knocking down BECN1 can significantly improve the movement and invasion of CRC cellsGene enrichment analysis (GSEA) through bioinformatics showed that the low expression level of BECN1 was significantly related to the STAT3 signaling pathway in CRCConsistently, knockout of the BECN1 gene increases the phosphorylation level of STAT3 in CRC cells and activates the STAT3 signaling pathwayin addition, the researchers confirmed that STAT3 was involved in the CRC transfer effect of internal and external source knocking low BECN1The mechanism study found that knocking out BECN1 promotes phosphorylation of STAT3 by regulating the interaction between STAT and JAK2, but does not inhibit the occurrence of autophagy in the cellstudies have shown that BECN1 can regulate the activation of the STAT3 signaling pathway by means of autophagy non-dependency and act as a negative regulator for the metastasis process of colorectal cancerTherefore, the BECN1/JAK2/STAT3 signaling pathway may be a potential therapeutic target for metastatic colorectal cancer