Golgi Phosphoprotein 2 Down-regulates the Th1 Response in Human Gastric Cancer Cells by Suppressing IL-12A

Tang, Qingfeng; Ji, Qing; Tang, Yu; Hu, Song-Jiao; Bao, Yi-Jie; Peng, Wen; Yin, Peihao

doi:10.7314/apjcp.2013.14.10.5747

Cited by 8 publications

(21 citation statements)

References 28 publications

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“…In our study, we found that the secreted GOLPH2 by malignant B cells inhibited IL-12 production from DCs and decreased IFN-g production by activated T cells indirectly via modulating the activity of DCs. Our data in the present study are consistent with the previous report that GOLPH2 overexpression inhibited IL-12 p35 transcription and IFN-g synthesis in human gastric cancer cells (46). Besides, we showed that GOLPH2's ability to suppress IL-12 production is independent of TGF-b, IL-10, TNF-a, and PGE 2 , all well-known inhibitors of IL-12 synthesis (data not shown).…”

Section: Discussionsupporting

confidence: 93%

Golgi Phosphoprotein 2 Is a Novel Regulator of IL-12 Production and Macrophage Polarization

Zhang

Kim

et al. 2018

The Journal of Immunology

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Golgi phosphoprotein 2 (GOLPH2), a widely expressed Golgi type II transmembrane protein, has been implicated in several important physiological and pathological processes, including virus infections, cancer cell proliferation, and metastasis. However, its biological functions and mechanisms, particularly in the immune system, remain highly obscure. In this study, we report the biochemical identification of GOLPH2 from B cell lymphoma culture supernatant and show that the secreted protein could inhibit IL-12 production by dendritic cells (DCs) and IL-12-induced IFN-γ production by activated T cells. Further molecular analysis revealed that GOLPH2's IL-12-inhibiting activity was mediated through a proximal promoter element involving a previously identified transcriptional repressor named GC-binding protein that is induced during phagocytosis of apoptotic cells by macrophages. We subsequently generated global knockout mice, which exhibited little developmental abnormality but were more susceptible to LPS-induced endotoxic shock than were wild-type mice with elevated serum IL-12 levels. Furthermore, we found that GOLPH2 played a regulatory role in macrophage polarization toward the M2 type. A comprehensive analysis of gene expression profiles of activated wild-type and GOLPH2-deficient DCs by RNA sequencing uncovered mechanistic insights into the way GOLPH2 potentially modulates DC function during inflammatory insults. Our functional study of GOLPH2 helps advance the scientific understanding of the biological and pathogenic roles of this novel and intriguing molecule with great potential as a diagnostic and prognostic marker as well as a therapeutic target in many acute and chronic inflammatory disorders.

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Section: Discussionsupporting

confidence: 93%

Golgi Phosphoprotein 2 Is a Novel Regulator of IL-12 Production and Macrophage Polarization

Zhang

Kim

et al. 2018

The Journal of Immunology

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“…GOLM1 is also a kind of secreted protein and is secreted form can be detected in both blood and urine. Bachert et al found that the proprotein convertase site R 52 VRR 55 was present in the GOLM1 protein sequence (Figure 1) [15]. During the Golgi-to-endosome transport process, GOLM1 is cleaved by the furin precursor protease to form a secreted protein separating from the transmembrane region.…”

Section: Expression Distribution and Subcellular Localization Of Golm1mentioning

confidence: 99%

“…They mainly enhance the initiation and expansion of CD8 + T cells by secreting IFN-γ and chemokines and recruit natural killer cells and Type I macrophages to tumor sites to eradicate tumors [50][51][52][53][54]. Tang et al found that GOLM1 may inhibit the tumor suppressor effect of Th1 cells in cancer tissues by downregulating the expression of IL-12A [55], which might provide a new target for the prevention and treatment of tumor. Kim et al speculated that the sGOLM1 in HCC may have a pathological effect in inhibiting IL-12 production by dendritic cells to prevent T cells from responding to malignant development [56].…”

Section: Role Of Golm1 In the Immune Systemmentioning

confidence: 99%

Recent advances of GOLM1 in hepatocellular carcinoma

Yan

Zhou

et al. 2020

Hepat. Oncol.

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Hepatocellular carcinoma (HCC) is one of the most common liver malignancies and is a leading cause of cancer-related deaths. Most HCC patients are diagnosed at an advanced stage and current treatments show poor therapeutic efficacy. It is particularly urgent to explore early diagnosis methods and effective treatments of HCC. There are a growing number of studies that show GOLM1 is one of the most promising markers for early diagnosis and prognosis of HCC. It is also involved in immune regulation, activation and degradation of intracellular signaling factors and promotion of epithelial–mesenchymal transition. GOLM1 can promote HCC progression and metastasis. The understanding of the GOLM1 regulation mechanism may provide new ideas for the diagnosis, monitoring and treatment of HCC.

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“…In line with in vitro studies, Corte et al reported a positive correlation between MMP-13 expression and MR in clinical melanoma tissue samples [35]. In their study on gastric cancer, Tang et al showed that GOLPH2 overexpression attenuated anti-tumor Th1 lymphocyte response [36]. This effect is likely to apply to melanoma, in which Th1-type immune response is a key defensive mechanism.…”

Section: Discussionmentioning

confidence: 91%

Golgi-Related Proteins GOLPH2 (GP73/GOLM1) and GOLPH3 (GOPP1/MIDAS) in Cutaneous Melanoma: Patterns of Expression and Prognostic Significance

Donizy

Kaczorowski

Biecek

et al. 2016

IJMS

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GOLPH2 and GOLPH3 are Golgi-related proteins associated with aggressiveness and progression of a number of cancers. Their prognostic significance in melanoma has not yet been analyzed. We performed immunohistochemical analysis for GOLPH2 and GOLPH3 in 20 normal skin, 30 benign nevi and 100 primary melanoma tissue samples and evaluated their expression in three compartments: cancer cells, tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs). High levels of both proteins in melanoma cells were associated with characteristics of aggressive disease, and shorter disease-free survival (DFS) and cancer-specific overall survival (CSOS). On the contrary, increased numbers of GOLPH2-positive and GOLPH3-positive TAMs were observed in thinner, non-ulcerated tumors, with brisk lymphocytic reaction and absent lymphangioinvasion. Distant metastases were not observed among patients with high numbers of GOLPH2-positive TAMs. Increased expression of either protein in TAMs was related to prolonged CSOS and DFS. Similarly, GOLPH3-expressing CAFs were more frequent in thin melanomas with low mitotic rate, without ulceration and lymphangioinvasion. Moreover, increased GOLPH3-positive CAFs correlated with the absence of regional or distant metastases, and with longer CSOS and DFS. GOLPH2 expression was not observed in CAFs. Our results suggest that GOLPH2 and GOLPH3 play a role in melanoma progression and are potential targets for molecular-based therapies.

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Golgi Phosphoprotein 2 Down-regulates the Th1 Response in Human Gastric Cancer Cells by Suppressing IL-12A

Cited by 8 publications

References 28 publications

Golgi Phosphoprotein 2 Is a Novel Regulator of IL-12 Production and Macrophage Polarization

Golgi Phosphoprotein 2 Is a Novel Regulator of IL-12 Production and Macrophage Polarization

Recent advances of GOLM1 in hepatocellular carcinoma

Golgi-Related Proteins GOLPH2 (GP73/GOLM1) and GOLPH3 (GOPP1/MIDAS) in Cutaneous Melanoma: Patterns of Expression and Prognostic Significance

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