Istituto di Biologia e Patologia Molecolari del CNR (CNR-IBPM), Roma, Italy.
Technol Cancer Res Treat. 2022 Jan-Dec;21:15330338221135724. doi: 10.1177/15330338221135724.
Golgi phosphoprotein 3 (GOLPH3), a highly conserved phosphatidylinositol 4-phosphate effector, is required for maintenance of Golgi architecture, vesicle trafficking, and Golgi glycosylation. GOLPH3 overexpression has been reported in several human solid cancers, including glioblastoma, breast cancer, colorectal cancer, nonsmall cell lung cancer, epithelial ovarian cancer, prostate cancer, gastric cancer, and hepatocellular carcinoma. Although the molecular mechanisms that link GOLPH3 to tumorigenesis require further investigation, it is likely that GOLPH3 may act by controlling the intracellular movement of key oncogenic molecules, between the Golgi compartments and/or between the Golgi and the endoplasmic reticulum. Indeed, numerous evidence indicates that deregulation of intracellular vesicle trafficking contributes to several aspects of cancer phenotypes. However, a direct and clear link between extracellular vesicle movements and GOLPH3 is still missing. In the past years several lines of evidence have implicated GOLPH3 in the regulation of extracellular vesicle content. Specifically, a new role for GOLPH3 has emerged in controlling the internalization of exosomes containing either oncogenic proteins or noncoding RNAs, especially micro-RNA. Although far from being elucidated, growing evidence indicates that GOLPH3 does not increase quantitatively the excretion of exosomes, but rather regulates the exosome content. In particular, recent data support a role for GOLPH3 for loading specific oncogenic molecules into the exosomes, driving both tumor malignancy and metastasis formation. Additionally, the older literature indirectly implicates GOLPH3 in cancerogenesis through its function in controlling hepatitis C virus secretion, which in turn is linked to hepatocellular carcinoma formation. Thus, GOLPH3 might promote tumorigenesis in unexpected ways, involving both direct and indirect routes. If these data are further confirmed, the spectrum of action of GOLPH3 in tumor formation will significantly expand, indicating this protein as a strong candidate for targeted cancer therapy.
高尔基体磷蛋白 3（GOLPH3）是一种高度保守的磷脂酰肌醇 4-磷酸效应物，对于维持高尔基体结构、囊泡运输和高尔基体糖基化是必需的。已经在几种人类实体瘤中报道了 GOLPH3 的过表达，包括神经胶质瘤、乳腺癌、结直肠癌、非小细胞肺癌、上皮性卵巢癌、前列腺癌、胃癌和肝细胞癌。虽然将 GOLPH3 与肿瘤发生联系起来的分子机制需要进一步研究，但 GOLPH3 可能通过控制关键致癌分子在高尔基体隔室之间和/或高尔基体与内质网之间的细胞内运动来发挥作用。事实上，大量证据表明细胞内囊泡运输的失调有助于癌症表型的几个方面。然而，细胞外囊泡运动与 GOLPH3 之间的直接和明确联系仍然缺失。在过去的几年中，有几条证据表明 GOLPH3 参与了细胞外囊泡内容物的调节。具体而言，GOLPH3 出现了一种新的作用，即控制含有致癌蛋白或非编码 RNA（特别是 microRNA）的外泌体的内化。尽管还远未阐明，但越来越多的证据表明 GOLPH3 不会增加外泌体的排泄量，而是调节外泌体的内容物。特别是，最近的数据支持 GOLPH3 将特定的致癌分子加载到外泌体中，从而驱动肿瘤恶性程度和转移形成的作用。此外，较早的文献通过其在控制丙型肝炎病毒分泌中的功能间接暗示了 GOLPH3 在癌症发生中的作用，而丙型肝炎病毒的分泌又与肝细胞癌的形成有关。因此，GOLPH3 可能以意想不到的方式促进肿瘤发生，包括直接和间接途径。如果这些数据得到进一步证实，GOLPH3 在肿瘤形成中的作用范围将显著扩大，表明该蛋白是癌症靶向治疗的一个强有力的候选物。
