Promotes the Growth and Metastasis of Colorectal Cancer by Activating E-Cadherin/Krüppel-Like Factor 4/Integrin α5 Signaling in a Calcium-Dependent Manner.

Gut microbiota and integrins are known to contribute to colorectal cancer (CRC), but whether they interact has been unclear. Here, we provided evidence that upregulated integrin α5 (ITGA5) in CRC in both human patients and murine models. Knocking down in CRC cells weakened the ability of to stimulate their malignant characteristics. increased intracellular Ca concentration, which in turn promoted interaction between E-cadherin and Krüppel-like factor 4 (KLF4), resulting in KLF4 phosphorylation and translocation in the nucleus, where it induced transcription and activated the downstream signaling. Knocking down E-cadherin or chelating Ca with BAPTA-AM antagonized the impact of on KLF4, whereas knocking down or chelating Ca antagonized the bacteria's oncogenic role. Knocking down or attenuated induced growth of patient-derived organoids, subcutaneous xenografts, and orthotopic tumors, as well as liver metastasis in nude mice. Integrin α5 antibody antagonized the oncogenic role of in vitro and in vivo. These findings suggest that promotes the growth and metastasis of CRC by activating E-cadherin/KLF4/integrin α5 signaling in a Ca-dependent manner.