Abstract
Golgi phosphoprotein 3 (GOLPH3), a Phosphatidylinositol 4-Phosphate [PI(4)P] effector at the Golgi, is required for Golgi ribbon structure maintenance, vesicle trafficking and Golgi glycosylation. GOLPH3 has been validated as an oncoprotein through combining integrative genomics with clinopathological and functional analyses. It is frequently amplified in several solid tumor types including melanoma, lung cancer, breast cancer, glioma, and colorectal cancer. Overexpression of GOLPH3 correlates with poor prognosis in multiple tumor types including 52% of breast cancers and 41% to 53% of glioblastoma. Roles of GOLPH3 in tumorigenesis may correlate with several cellular activities including: (i) regulating Golgi-to-plasma membrane trafficking and contributing to malignant secretory phenotypes; (ii) controlling the internalization and recycling of key signaling molecules or increasing the glycosylation of cancer relevant glycoproteins; and (iii) influencing the DNA damage response and maintenance of genomic stability. Here we summarize current knowledge on the oncogenic pathways involving GOLPH3 in human cancer, GOLPH3 influence on tumor metabolism and surrounding stroma, and its possible role in tumor metastasis formation.
Highlights
Golgi phosphoprotein 3 (GOLPH3), a Phosphatidylinositol 4-Phosphate [PI(4)P] effector at the Golgi, is required for Golgi ribbon structure maintenance, vesicle trafficking and Golgi glycosylation
An increasing number of papers has shown that GOLPH3 drives cancer in several other solid tumors such as Neuroblastoma (NB) [42], Non-Small Cell Lung Cancer (NSLC) [89], epithelial ovarian carcinoma [90], prostate cancer [91,92], gastric cancer [93], and hepatocellular carcinoma [94,95] (Figure 2)
Experimental data in cancer cell lines or in nude mice revealed the role of GOLPH3 in cell proliferation, metastasis formation and angiogenesis (Figure 2)
Summary
The oncogenic secretion properties of GOLPH3 are not limited to its role in anterograde Golgi-to-PM trafficking Another route through which GOLPH3 is thought to influence cell transformation, is the retrograde intra-Golgi trafficking of protein glycosyltransferases (Figure 1) [10,25,34]. Isaji et al [36] demonstrated the importance of GOLPH3-dependent sialylation on N-glycans, including those on β1-integrins, and reported that overexpression of α2,6-sialyltransferase-I (SiaT) is able to rescue integrin-dependent cell migration alterations caused by GOLPH3 depletion (Figure 1). Altered glycan structures can influence endocytosis and recycling of transmembrane receptors resulting in prolonged growth factor signaling [3] Taken together, these data indicate that the role of GOLPH3 in glycosylation is an important aspect of its oncogenic properties
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