Golgi phosphoprotein 3 induces autophagy and epithelial–mesenchymal transition to promote metastasis in colon cancer

• Published in: Cell death discovery Vol. 8; no. 1; p. 76
• Main Authors: Gong, Li-Yun, Tu, Ting, Zhu, Jing, Hu, Ao-Ping, Song, Jun-Wei, Huang, Jing-Qiang, Yang, Yi, Zhu, Zeyao, Chen, Yu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21-02-2022; Springer Nature B.V; Nature Publishing Group
• Subjects: 1-Phosphatidylinositol 3-kinase; 631/67/322; 692/53/2422; AKT protein; Apoptosis; Autophagy; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cell culture; Cell Cycle Analysis; Colon cancer; Colorectal cancer; Golgi apparatus; Immunohistochemistry; Kinases; Life Sciences; Mesenchyme; Metastases; Metastasis; Phosphorylation; Ribonucleic acid; RNA; Stem Cells; Western blotting; Wound healing
• ISSN: 2058-7716; 2058-7716
• DOI: 10.1038/s41420-022-00864-2

In this study, we aimed to investigate whether and how Golgi phosphoprotein 3 (GOLPH3) facilitates colon cancer metastasis via the regulation of autophagy and epithelial–mesenchymal transition (EMT). The role GOLPH3 plays in colon cancer metastasis was analyzed using western blotting, immunohistochemistry, transwell, wound-healing, and zebrafish assays. Autophagy and EMT were assessed via RNA-sequencing (RNA-seq) analysis, mRFP-GFP-LC3 reporter assays, and their related markers. Significant associations were found between colon cancer clinical and pathological stages and poor prognosis. GOLPH3 facilitates colon cancer metastasis, both in vitro and in vivo. RNA-seq analysis of GOLPH3-overexpressing and control cell models revealed that GOLPH3 enhances EMT and autophagy. Moreover, examination of autophagic, epithelial, and mesenchymal markers in GOLPH3-overexpressing, -silenced, and control cell lines revealed that GOLPH3 promotes EMT and autophagy. When autophagy was inhibited, GOLPH3-promoted metastasis and EMT were counteracted in vitro and in vivo. Using RNA-seq, PI3K/Akt signaling was identified as the key downstream pathway on which GOLPH3 acts. Mechanistically, we demonstrated that GOLPH3 stimulates autophagy and induces EMT via the suppression of the phosphorylation of protein kinase B (Akt) at Ser473. In summary, GOLPH3 induces autophagy and EMT, promoting metastasis in colon cancer. Beyond this, and in contrast to conventional perspectives, we discovered that GOLPH3 represses the phosphorylation of Akt at Ser473.