The multiple cellular functions of the oncoprotein Golgi phosphoprotein 3

Sechi, Stefano; Frappaolo, Anna; Belloni, Giorgio; Colotti, Gianni; Giansanti, Maria Grazia

doi:10.18632/oncotarget.3051

Cited by 49 publications

(66 citation statements)

References 108 publications

(210 reference statements)

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“…In addition, GOLPH3 plays an important role in integrin-mediated cell migration via the up-regulation of sialylation [8], which suggests that GOLPH3 might regulate the progression of the tumors through its biological roles of glycosylation. Although it is generally accepted that the GOLPH3 has been implicated in retrograde trafficking of vesicles routed towards the Golgi [9], some studies reported that many receptors (e.g. transferrin receptor) recycle from perinuclear/trans Golgi region via recycling endosomes rather than getting into the constitutive secretory traffic [44,45].…”

Section: Discussionmentioning

confidence: 99%

Golgi Phosphoprotein 3 Promotes Wls Recycling and Wnt Secretion in Glioma Progression

Lu¹,

Zhang²,

Fu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Golgi phosphoprotein 3 (GOLPH3) plays pro-malignancy roles in several types of cancer. However, the molecular mechanism underlying GOLPH3 promoting tumor progression remains poorly understood. Methods: The expression of GOLPH3 and Wntless (Wls) in glioma tissues was examined by western blotting and immunohistochemistry. EdU incorporation assay and colony formation assay was used to examine the cell growth ability. The effect of GOLPH3 on Wls recycling, Wnt secretion and β-catenin activity was detected using western blotting, immunofluorescence, RT-PCR, ELISA or luciferase assay. Results: The protein levels of GOLPH3 and Wls were upregulated and positively correlated with each other in human glioma tissues. The promoting effect of GOLPH3 on glioma cell proliferation was partially mediated by Wls. In addition, GOLPH3 interacted with Wls and GOLPH3 down-regulation drove Wls into lysosome for degradation, inhibiting its recycling to golgi and the plasma membrane. Importantly, GOLPH3 down-regulation inhibited Wnt2b secretion and decreased β-catenin level and transcription activity. Conclusions: This study provides a brand new evidence that GOLPH3 promotes glioma cell proliferation by facilitating Wls recycling and Wnt/β-catenin signaling. Our findings suggest a rationale for targeting the GOLPH3-Wls-Wnt axis as a promising therapeutic approach for glioblastoma.

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Section: Discussionmentioning

confidence: 99%

Golgi Phosphoprotein 3 Promotes Wls Recycling and Wnt Secretion in Glioma Progression

Lu¹,

Zhang²,

Fu³

et al. 2018

Cell Physiol Biochem

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“…iii) Apart from GOLPH3, other proteins from the GOLPH family, such as GOLPH2, were identified to be ectopically expressed in GCs (27). iv) Even though a full underlying molecular mechanism was not observed, GOLPH3 was proven to play an essential role in vesicle trafficking and Golgi structure (28). Moreover, Field et al found that overexpression of GOLPH3 confers resistance to killing by DNA-damaging agents and depletion of GOLPH3 could enhance the ability of DNA-damaging agents to kill cells (29).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-134 suppresses cell proliferation in gastric cancer cells via targeting of GOLPH3

2017

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Emerging evidence has shown that microRNAs (miRNAs) play critical roles in tumor development and progression. miR-134 has been found to act as a tumor-suppressor in numerous types of cancers. However, little is known concerning the potential role of miR-134 in gastric carcinogenesis. In the present study, we found that miR-134 was highly downregulated in gastric cancer tissues and cell lines when compared with levels in their adjacent non-tumor tissues and the normal human gastric epithelial cell line GES-1. Additionally, overexpression of miR-134 was accompanied by reduced cell proliferation in vitro and decreased tumor size in vivo. Further investigation by luciferase reporter assay indicated that Golgi phosphoprotein 3 (GOLPH3), a potent oncogene, was a direct target of miR-134. The activity of a luciferase reporter carrying the miR-134 binding site in the 3'-untranslated region (3'-UTR) of GOLPH3 was repressed by overexpression of miR-134, while a mutation in the 3'-UTR of GOLPH3 abrogated this effect, indicating that GOLPH3 is a target gene of miR-134. Overexpression of GOLPH3 blocked the antiproliferative effect of pre-miR-134 in gastric carcinoma cells. Furthermore, overexpression of miR-134 was associated with decreased phosphorylation of AKT, mTOR and S6K. Taken together, these data suggest that miR-134 regulates gastric cancer cell proliferation, at least potentially, through downregulation of the GOLPH3 gene, implicating a candidate tumor-suppressor miRNA in the pathogenesis of gastric cancer.

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“…The oncogenic activity of GOLPH3 has been primarily correlated with its ability to influence signaling downstream of the mammalian target of rapamycin (mTOR), resulting in enhanced activation of both mammalian TORC1 and TORC2 complexes [9,10]. This idea was supported by preclinical treatment studies showing that GOLPH3-expressing tumors are much more sensitive to mTOR inhibitors, raising the possibility that GOLPH3 levels might predict rapamycin efficacy in tumor therapy.…”

Section: The Pi(4)p Binding Protein Golph3 Is An Oncoproteinmentioning

confidence: 99%

Oncogenic Roles of GOLPH3 in the Physiopathology of Cancer

Sechi

Frappaolo

Karimpour-Ghahnavieh

et al. 2020

IJMS

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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.

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The multiple cellular functions of the oncoprotein Golgi phosphoprotein 3

Cited by 49 publications

References 108 publications

Golgi Phosphoprotein 3 Promotes Wls Recycling and Wnt Secretion in Glioma Progression

Golgi Phosphoprotein 3 Promotes Wls Recycling and Wnt Secretion in Glioma Progression

MicroRNA-134 suppresses cell proliferation in gastric cancer cells via targeting of GOLPH3

Oncogenic Roles of GOLPH3 in the Physiopathology of Cancer

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