GOLPH3-mTOR Crosstalk and Glycosylation: A Molecular Driver of Cancer Progression

Originally identified in proteomic-based studies of the Golgi, Golgi phosphoprotein 3 (GOLPH3) is a highly conserved protein from yeast to humans. GOLPH3 localizes to the Golgi through the interaction with phosphatidylinositol-4-phosphate and is required for Golgi architecture and vesicular trafficking. Many studies revealed that the overexpression of GOLPH3 is associated with tumor metastasis and a poor prognosis in several cancer types, including breast cancer, glioblastoma multiforme, and colon cancer. The purpose of this review article is to provide the current progress of our understanding of GOLPH3 molecular and cellular functions, which may potentially reveal therapeutic avenues to inhibit its activity. Specifically, recent papers have demonstrated that GOLPH3 protein functions as a cargo adaptor for COP I-coated intra Golgi vesicles and impinges on Golgi glycosylation pathways. In turn, GOLPH3-dependent defects have been associated with malignant phenotypes in cancer cells. Additionally, the oncogenic activity of GOLPH3 has been linked with enhanced signaling downstream of mechanistic target of rapamycin (mTOR) in several cancer types. Consistent with these data, GOLPH3 controls organ growth in Drosophila by associating with mTOR signaling proteins. Finally, compelling evidence demonstrates that GOLPH3 is essential for cytokinesis, a process required for the maintenance of genomic stability.