Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is increasingly recognized that chimeric RNAs may exert a novel layer of cellular complexity that contributes to oncogenesis and cancer progression, and could be utilized as molecular biomarkers and therapeutic targets. To date yet no fusion chimeric RNAs have been identified in esophageal cancer, the 6th most frequent cause of cancer death in the world. While analyzing the expression of 32 recurrent cancer chimeric RNAs in esophageal squamous cell carcinoma (ESCC) from patients and cancer cell lines, we identified GOLM1-MAK10, as a highly cancer-enriched chimeric RNA in ESCC. In situ hybridization revealed that the expression of the chimera is largely restricted to cancer cells in patient tumors, and nearly undetectable in non-neoplastic esophageal tissue from normal subjects. The aberrant chimera closely correlated with histologic differentiation and lymph node metastasis. Furthermore, we demonstrate that chimera GOLM1-MAK10 encodes a secreted fusion protein. Mechanistic studies reveal that GOLM1-MAK10 is likely derived from transcription read-through/splicing rather than being generated from a fusion gene. Collectively, these findings provide novel insights into the molecular mechanism involved in ESCC and provide a novel potential target for future therapies. The secreted fusion protein translated from GOLM1-MAK10 could also serve as a unique protein signature detectable by standard non-invasive assays. These observations are critical as there is no clinically useful molecular signature available for detecting this deadly disease or monitoring the treatment response.
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PMID:Aberrant chimeric RNA GOLM1-MAK10 encoding a secreted fusion protein as a molecular signature for human esophageal squamous cell carcinoma. 2424 30

Non-small-cell carcinoma (NSCLC) is one of the most lethal malignancies of lung cancers and its prognosis remains dismal due to the paucity of effective therapeutic targets. Recent reports show that Golgi membrane protein 1 (GOLM1) is highly expressed in a variety of tumor cells, functions as a negative regulator of T cells and then promotes tumor progression. However, its expression and role in NSCLC remain unclear. Herein, we showed that GOLM1 was markedly up-regulated in NSCLC cell lines and clinical tissues. Clinically, NSCLC patients with high expression of GOLM1 had shorter overall survival (OS) and high GOLM1 expression in tumor samples was significantly related to malignant phenotype, such as lymph node metastasis and high tumor stage. Ectopic expression of GOLM1 in NSCLC cells induced epithelial-to-mesenchymal transition (EMT) and promoted proliferation, migration, and invasion of NSCLC cells in vitro. Furthermore, GOLM1 overexpressing significantly promoted the tumorigenicity of NSCLC cells in vivo whereas silencing endogenous GOLM1 caused an opposite outcome. Moreover, we demonstrated that GOLM1 enhanced NSCLC aggressiveness by activating matrix metalloproteinase-13 (MMP13) signaling. Together, our results provided new evidence that GOLM1 overexpression promoted the progression of NSCLC and might represent a novel therapeutic target for its treatment.
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PMID:Overexpression of golgi membrane protein 1 promotes non-small-cell carcinoma aggressiveness by regulating the matrix metallopeptidase 13. 2963 8

Extracellular vesicles (EVs) mediate critical intercellular communication within healthy tissues, but are also exploited by tumour cells to promote angiogenesis, metastasis, and host immunosuppression under hypoxic stress. We hypothesize that hypoxic tumours synthesize hypoxia-sensitive proteins for packing into EVs to modulate their microenvironment for cancer progression. In the current report, we employed a heavy isotope pulse/trace quantitative proteomic approach to study hypoxia sensitive proteins in tumour-derived EVs protein. The results revealed that hypoxia stimulated cells to synthesize EVs proteins involved in enhancing tumour cell proliferation (NRSN2, WISP2, SPRX1, LCK), metastasis (GOLM1, STC1, MGAT5B), stemness (STC1, TMEM59), angiogenesis (ANGPTL4), and suppressing host immunity (CD70). In addition, functional clustering analyses revealed that tumour hypoxia was strongly associated with rapid synthesis and EV loading of lysosome-related hydrolases and membrane-trafficking proteins to enhance EVs secretion. Moreover, lung cancer-derived EVs were also enriched in signalling molecules capable of inducing epithelial-mesenchymal transition in recipient cancer cells to promote their migration and invasion. Together, these data indicate that lung-cancer-derived EVs can act as paracrine/autocrine mediators of tumorigenesis and metastasis in hypoxic microenvironments. Tumour EVs may, therefore, offer novel opportunities for useful biomarkers discovery and therapeutic targeting of different cancer types and at different stages according to microenvironmental conditions.
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PMID:Microenvironmental Hypoxia Induces Dynamic Changes in Lung Cancer Synthesis and Secretion of Extracellular Vesicles. 3305 Jun 15

GOLM1, a type II transmembrane protein, is associated with tumor progression, metastasis and immunosuppression. However, the relationship between GOLM1 and the immunosuppressive molecule PD-L1 in HCC remains largely unclear. Here, we revealed that GOLM1 acts as a novel positive regulator of PD-L1, whose abnormal expression plays a crucial role in cancer immune evasion and progression. We found that GOLM1 is overexpressed and positively correlated with PD-L1 expression in HCC. Mechanistically, we found that GOLM1 promotes the phosphorylation of STAT3 by enhancing the level of EGFR, which in turn upregulates the transcriptional expression of PD-L1. Taken together, we demonstrated that GOLM1 acts as a positive regulator of PD-L1 expression via the EGFR/STAT3 signaling pathway in human HCC cells. This study provides a new insight into the regulatory mechanism of PD-L1 expression in HCC, which may provide a novel therapeutic target for HCC immunotherapy.
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PMID:GOLM1 upregulates expression of PD-L1 through EGFR/STAT3 pathway in hepatocellular carcinoma. 3329 62