Istituto di Biologia e Patologia Molecolari del CNR, Dipartimento di Biologia e Biotecnologie, Sapienza Università di Roma, 00185 Roma, Italy.
Int J Mol Sci. 2020 Jan 31;21(3):933. doi: 10.3390/ijms21030933.
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.
高尔基磷蛋白 3（GOLPH3）是高尔基体上的磷酸肌醇 4-磷酸[PI（4）P]效应物，对于维持高尔基体带结构、囊泡运输和高尔基体糖基化是必需的。通过整合基因组学与临床病理和功能分析，已经验证 GOLPH3 是一种癌蛋白。它在几种实体肿瘤类型中经常扩增，包括黑色素瘤、肺癌、乳腺癌、神经胶质瘤和结直肠癌。GOLPH3 的过表达与多种肿瘤类型的不良预后相关，包括 52%的乳腺癌和 41%至 53%的神经胶质瘤。GOLPH3 在肿瘤发生中的作用可能与几种细胞活动相关，包括：（i）调节高尔基体到质膜的运输，并有助于恶性分泌表型；（ii）控制关键信号分子的内化和循环，或增加与癌症相关糖蛋白的糖基化；以及（iii）影响 DNA 损伤反应和基因组稳定性的维持。在这里，我们总结了涉及人类癌症中 GOLPH3 的致癌途径、GOLPH3 对肿瘤代谢和周围基质的影响以及它在肿瘤转移形成中的可能作用的现有知识。
