GOLM1 depletion modifies cellular sphingolipid metabolism and adversely affects cell growth

Nagaraj, Meghana; Höring, Marcus; Ahonen, Maria A.; Nguyen, Van Dien; Zhou, You; Vihinen, Helena; Jokitalo, Eija; Liebisch, Gerhard; Haridas, Parvathi; Olkkonen, Vesa M.

doi:10.1016/j.jlr.2022.100259

Cited by 8 publications

(9 citation statements)

References 61 publications

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“…30 At the cellular level, transient siRNA silencing of GOLM1 in Huh-7 cells (a HCC derived cell line) resulted in a scattered Golgi ultrastructure, a lower mitochondrial oxygen consumption rate, an increased presence of ceramides and other sphingolipids, reduced cell proliferation, and increased apoptosis. 31 In line with this, overexpression of GOLM1 in PC9 cells promoted cell proliferation, migration and invasion. 32 Moreover, depletion of GOLM1 in intestinal epithelial cells led to aberrant NOTCH signaling that interfered with cell differentiation and maturation.…”

Section: Properties and Functions Of Golm1mentioning

confidence: 64%

“…Moreover, the liver and kidney of these mice showed pathological changes, such as focal segmental glomerulosclerosis and hepatocyte nuclear membrane irregularities, which suggest that GOLM1 plays a role in the function of these organs 30 . At the cellular level, transient siRNA silencing of GOLM1 in Huh‐7 cells (a HCC derived cell line) resulted in a scattered Golgi ultrastructure, a lower mitochondrial oxygen consumption rate, an increased presence of ceramides and other sphingolipids, reduced cell proliferation, and increased apoptosis 31 . In line with this, overexpression of GOLM1 in PC9 cells promoted cell proliferation, migration and invasion 32 .…”

Section: Properties and Functions Of Golm1mentioning

confidence: 81%

“…Although no interactions of GOLM1 with cytokines have been reported, it seems possible that GOLM1 affects their trafficking indirectly for two reasons. First, the ablation of GOLM1 has been shown to result in a scattered Golgi ultrastructure, 31 which is highly likely to impact Golgi trafficking 54 . Second, GOLM1 was found by mass spectrometry to interact with SNAREs, small‐GTPases of the Rab family, and other trafficking proteins with well‐known roles in Golgi transport, 23 and this can also be expected to broadly impact Golgi trafficking.…”

Section: Discussionmentioning

confidence: 99%

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Unveiling the impact of GOLM1/GP73 on cytokine production in cancer and infectious disease

et al. 2023

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The Golgi membrane protein GOLM1/GP73/GOLPH2 has been found to impact cytokine production in both infectious disease and cancer. In viral infections, GOLM1 levels are increased, and this lowers the production of type I interferons and other inflammatory cytokines. However, elevated GOLM1 expression levels due to mutations are linked to a higher production of interleukin (IL)‐6 during Candida infections, potentially explaining an increased susceptibility to candidemia in individuals carrying these mutations. In cancer, the protease Furin produces a soluble form of GOLM1 that has oncogenic properties by promoting the production of the chemokine CCL2 and suppressing the production of inflammatory cytokines such as IL‐12 and interferon gamma. This review will focus on the role of GOLM1 in cytokine production, highlighting how it can both promote and inhibit cytokine production. It is crucial to understand this in order to effectively target GOLM1 for therapeutic purposes in diseases associated with abnormal cytokine production, including cancer and infectious disease.

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Section: Properties and Functions Of Golm1mentioning

confidence: 64%

Section: Properties and Functions Of Golm1mentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

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Unveiling the impact of GOLM1/GP73 on cytokine production in cancer and infectious disease

et al. 2023

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“…27 GP73 participates in epithelial-mesenchymal transition, inflammatory response, lipid metabolism, and glucose homeostasis. [28][29][30][31][32] Yan et al 14 reported that GP73 activates the PI3K-AKT-mTOR signaling pathway to promote cell proliferation and invasion. GP73 promotes cell growth and metastasis via activating EGFR/RTK.…”

Section: Discussionmentioning

confidence: 99%

Golgi Protein 73 Promotes LPS-Induced Cardiac Dysfunction via Mediating Myocardial Apoptosis and Autophagy

Xing,

Gao,

Bai

et al. 2024

Journal of Cardiovascular Pharmacology

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Sepsis-induced cardiac dysfunction represents a major cause of high mortality in intensive care units with limited therapeutic options. Golgi protein 73 (GP73) has been implicated in various diseases. However, the role of GP73 in LPS-induced cardiac dysfunction is unclear. Here, we established sepsis-induced cardiac dysfunction model by LPS administration in wild type (WT) and GP73 knockout (GP73 -/- ) mice. We found GP73 was increased in LPS-treated mouse hearts and LPS-cultured neonatal rat cardiomyocytes (NRCMs). Knockout of GP73 alleviated myocardial injury and improved cardiac dysfunction. Moreover, depletion of GP73 in NRCMs relieved LPS-induced cardiomyocyte apoptosis and activated myocardial autophagy. Therefore, GP73 is a negative regulator in LPS-induced cardiac dysfunction by promoting cardiomyocyte apoptosis and inhibiting cardiomyocyte autophagy.

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“…For sphingolipid metabolism, Nagaraj et al found that GOLM1 depletion can affect cell proliferation by regulating cellular sphingolipid metabolism. 29 Biological enrichment analysis showed that the high-risk patients might have a higher pathway activity of G2M checkpoints, KRAS signalling and E2F targets. The G2/M checkpoint, a critical control point in the cell cycle, ensures proper DNA replication before cell division.…”

Section: Discussionmentioning

confidence: 99%

Identification of metabolism terms significantly affecting hepatocellular carcinoma immune microenvironment and immunotherapy response

Tan,

Chen,

Luo

et al. 2023

J Cellular Molecular Medi

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Metabolic pathways exert a significant influence on the onset and progression of cancer. Public data on hepatocellular carcinoma (HCC) patients were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Analysis was performed in R software using different R packages. Here, we integrated the data from multiple independent HCC cohorts, including TCGA‐LIHC, ICGC‐FR and ICGC‐JP. Then, the enrichment score of 21 metabolism‐related pathways was quantified using the ssGSEA algorithm. Next, univariate Cox regression analysis was applied to identify the metabolic terms with significant correlation to patient survival. Finally, a prognosis model based on linoleic acid metabolism, sphingolipid metabolism and regulation of lipolysis in adipocytes was established, which showed good performance in predicting patients' survival. Furthermore, we conducted a biological enrichment analysis to delineate the biological disparities between high‐ and low‐risk patients. Notably, we discerned differences in the microenvironments between these two patient groups. We also found that low‐risk patients could potentially respond better to immunotherapy. Drug sensitivity analysis suggested that low‐risk patients are more susceptible to bexarotene and erlotinib, yet exhibit resistance to ATRA and bleomycin. Furthermore, through the use of LASSO logistic regression analysis, we identified 19 characteristic genes, which could robustly indicate the risk groups. Our research underscores the role of linoleic acid metabolism, sphingolipid metabolism and the regulation of lipolysis in adipocytes in HCC, pointing towards potential avenues for future research.

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GOLM1 depletion modifies cellular sphingolipid metabolism and adversely affects cell growth

Cited by 8 publications

References 61 publications

Unveiling the impact of GOLM1/GP73 on cytokine production in cancer and infectious disease

Unveiling the impact of GOLM1/GP73 on cytokine production in cancer and infectious disease

Golgi Protein 73 Promotes LPS-Induced Cardiac Dysfunction via Mediating Myocardial Apoptosis and Autophagy

Identification of metabolism terms significantly affecting hepatocellular carcinoma immune microenvironment and immunotherapy response

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