Calcium‐binding protein 39 promotes hepatocellular carcinoma growth and metastasis by activating extracellular signal‐regulated kinase signaling pathway

Jiang, Lingxi; Yan, Qian; Fang, Shuo; Liu, Ming; Li, Yan; Yuan, Yunfei; Zhu, Ying–Hui; Qi, Jiali; Yang, Xiaodong; Kwong, Dora Lai Wan; Guan, Xin Yuan

doi:10.1002/hep.29312

Cited by 48 publications

(42 citation statements)

References 32 publications

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“…Both univariate and multivariate analyses also revealed that a high level of serum miR‐103 was an independent predictor for short recurrence‐free survival of HCC patients (Table ). Furthermore, cellular miR‐103 and secreted miR‐103 were detected at relatively high levels in two metastatic hepatoma cell lines (MHCC97H and QGY‐7703), at low levels in nonmetastatic HepG2 cells, and immortalized liver cell line LO2, and at extremely low level in HUVECs (Fig. B).…”

Section: Resultsmentioning

confidence: 99%

Hepatoma cell‐secreted exosomal microRNA‐103 increases vascular permeability and promotes metastasis by targeting junction proteins

et al. 2018

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Section: Resultsmentioning

confidence: 99%

Hepatoma cell‐secreted exosomal microRNA‐103 increases vascular permeability and promotes metastasis by targeting junction proteins

et al. 2018

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“…Both the MER/ERK and PI3K/AKT signaling pathway are involved in the regulation of tumor cell growth, metabolism, proliferation, as well as metastasis and are frequently proved to be active in many different types of cancer [ 32 ]. A recent report indicated that COMP could promote the process of liver fibrosis through MEK/ERK signaling pathway [ 4 ].…”

Section: Discussionmentioning

confidence: 99%

HSCs-derived COMP drives hepatocellular carcinoma progression by activating MEK/ERK and PI3K/AKT signaling pathways

Wang

et al. 2018

J Exp Clin Cancer Res

107

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BackgroundCartilage oligomeric matrix protein (COMP) is known to promote fibrosis in skin, lung and liver. Emerging evidence shows that COMP plays critical roles in tumor development, including breast cancer, colon cancer and hepatocellular carcinoma (HCC). Nevertheless, the role of COMP in HCC proliferation and metastasis and its underlying mechanisms remain fully unclear.MethodsSerum COMP was determined by ELISA. Cell Counting Kit-8 and plate colony formation were performed to evaluate cell proliferation. Wound healing and transwell assays were used to determine migration and invasion of HCC cells. Western blotting and immunofluorescence were carried out for detection of epithelial-to-mesenchymal transition (EMT) markers and MMPs in HCC cells. The in vivo role of COMP was evaluated using mouse models. We also measured effects of hepatic stellate cells (HSCs)-conditioned medium (CM) on HCC progression using transwell coculture system.ResultsHere, we found that serum COMP levels in HCC patients were significantly higher than those in healthy controls. Accordingly, high serum COMP levels in HCC patients significantly correlated with malignant clinical characteristics and poor clinical outcomes. Next, we investigated that recombinant human COMP protein (rCOMP) treatment resulted in increased abilities of proliferation, invasion and migration of HCC cells. Furthermore, rCOMP treatment enhanced proliferative and metastatic colonization of HCC cells in vivo. Mechanistically, CD36 receptor played an essential role in COMP-mediated HCC cell proliferation and metastasis. Functionally, COMP/CD36 signaling caused phosphorylation of ERK and AKT, resulting in the upregulation of tumor-progressive genes such as EMT markers, MMP-2/9, Slug and Twist in HCC cells. Interestingly, we revealed that COMP was secreted by HSCs. CM of LX2 cells with COMP knockdown showed weaker effects on the activation of MEK/ERK and PI3K/AKT signaling pathways in HCC cells compared to control CM.ConclusionsOur findings indicated that HSCs-derived COMP collaborated with CD36 and subsequently played an essential role in MEK/ERK and PI3K/AKT-mediated HCC progression. COMP might act as a promising target for the diagnosis and treatment of aggressive HCC.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0908-y) contains supplementary material, which is available to authorized users.

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“…In the combined populations, two positional candidate and 28 leading-edge genes were predicted to be regulated. The master regulator CAB39, previously identified as MO25, regulates protein kinases, and has been identified to be involved in cellular invasion and in both hepatic [101] and pancreatic cancers [102]. Further investigation of the role of CAB39 is needed to understand its impact on pregnancy loss.…”

Section: Master Regulators Shared In Two or More Populationsmentioning

confidence: 99%

Genomic Analysis of Spontaneous Abortion in Holstein Heifers and Primiparous Cows

Oliver

Wahl

Dick

et al. 2019

Genes

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Background: The objectives of this study were to identify loci, positional candidate genes, gene-sets, and pathways associated with spontaneous abortion (SA) in cattle and compare these results with previous human SA studies to determine if cattle are a good SA model for humans. Pregnancy was determined at gestation day 35 for Holstein heifers and cows. Genotypes from 43,984 SNPs of 499 pregnant heifers and 498 pregnant cows that calved at full term (FT) were compared to 62 heifers and 28 cows experiencing SA. A genome-wide association analysis, gene-set enrichment analysis-single nucleotide polymorphism, and ingenuity pathway analysis were used to identify regions, pathways, and master regulators associated with SA in heifers, cows, and a combined population. Results: Twenty-three loci and 21 positional candidate genes were associated (p < 1 × 10 −5 ) with SA and one of these (KIR3DS1) has been associated with SA in humans. Eight gene-sets (NES > 3.0) were enriched in SA and one was previously reported as enriched in human SA. Four master regulators (p < 0.01) were associated with SA within two populations. Conclusions: One locus associated with SA was validated and 39 positional candidate and leading-edge genes and 2 gene-sets were enriched in SA in cattle and in humans.

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Calcium‐binding protein 39 promotes hepatocellular carcinoma growth and metastasis by activating extracellular signal‐regulated kinase signaling pathway

Cited by 48 publications

References 32 publications

Hepatoma cell‐secreted exosomal microRNA‐103 increases vascular permeability and promotes metastasis by targeting junction proteins

Hepatoma cell‐secreted exosomal microRNA‐103 increases vascular permeability and promotes metastasis by targeting junction proteins

HSCs-derived COMP drives hepatocellular carcinoma progression by activating MEK/ERK and PI3K/AKT signaling pathways

Genomic Analysis of Spontaneous Abortion in Holstein Heifers and Primiparous Cows

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