G-protein signaling modulator 1 promotes colorectal cancer metastasis by PI3K/AKT/mTOR signaling and autophagy.

Abstract

Colorectal cancer is the second most common malignant tumor worldwide. A deeper insight into the mechanisms underlying colorectal cancer metastasis is urgently needed. G-protein signaling modulator 1 and autophagy play critical roles in tumor migration and invasion. However, the biological functions and regulatory networks of G-protein signaling modulator 1 and autophagy have not yet been fully studied. We performed immunohistochemistry and clinic-pathological characteristic analysis in 328 human colorectal cancer specimens to identify the clinical role of G-protein signaling modulator 1 in colorectal cancer. An in vitro coculture system and a tumor metastasis mouse model were used to explore the biological function of G-protein signaling modulator 1 on tumor metastasis. Autophagic flux detection like GFP-LC3B signal immunofluorescence and electron microscope observation of autophagic vesicles and confocal microscope detection were used to gain insights into the underlying role of G-protein signaling modulator 1 in autophagy. We found that G-protein signaling modulator 1 was abundantly expressed in colorectal cancer tissues and was associated with lymph node metastasis and poor prognosis. Furthermore, our bioinformatic and functional studies demonstrated that G-protein signaling modulator 1 significantly promoted cell migration and invasion, both in vitro and in vivo. Mechanistically, we demonstrated that G-protein signaling modulator 1 could promote colorectal cancer cell migration and invasion and inhibit autophagy and by activating the PI3K/AKT/mTOR pathway. We proposed that G-protein signaling modulator 1 promotes colorectal cancer metastasis by modulating autophagy through the PI3K/AKT/mTOR pathway.