Docosahexaenoic Acid Modulates Invasion and Metastasis of Human Ovarian Cancer via Multiple Molecular Pathways

Wang, Yingchun; Wu, Yan-Guang; Wang, Suli; Lin, Qing; He, Ming-Fang; Liu, Qiaolin; Wang, Jinhua

doi:10.1097/igc.0000000000000746

Cited by 16 publications

(11 citation statements)

References 32 publications

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“…It has been reported that DHA can inhibit EMT by suppressing the expression of α-smooth muscle actin in prostate fibroblasts [21]. Although DHA has been reported to be able to inhibit the metastasis of cancer cells [53][54][55][56], studies on molecular mechanisms by which DHA inhibits EMT are insufficient. Several studies have reported that BMP signaling can inhibit EMT.…”

Section: Discussionmentioning

confidence: 99%

DHA inhibits Gremlin-1-induced epithelial-to-mesenchymal transition via ERK suppression in human breast cancer cells

et al. 2020

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Docosahexaenoic acid (DHA) is an omega-3 fatty acid abundant in fish oils. It is known to have an inhibitory effect on various diseases such as inflammation, diabetes, and cancer. Epithelial-to-mesenchymal transition (EMT) is a process that epithelial cells gain migratory property to become mesenchymal cells involved in wound healing, organ fibrosis, and cancer progression. Gremlin-1 (GREM1) is a bone morphogenetic protein antagonist known to play a role in EMT. However, the role of GREM1 in the induction of EMT in human breast cancer cells and the effect of DHA on GREM1-induced EMT remain unclear. Establishment of GREM1 knockdown cell lines was performed using lentiviral shRNAs. Expression of EMT markers was determined by qRT-PCR and Western blotting. Effect of GREM1 and/or DHA on cell migration was investigated using wound healing assay. The level of GREM1 expression in human breast cancer tissues was determined by Oncomine database mining. GREM1 induced the expression of genes including N-cadherin, vimentin, and Slug. GREM1 promoted the migration of human breast cancer cells. GREM1 enhanced the expression of phosphorylated extracellular signal-regulated kinase (p-ERK) and the ERK activation was involved in EMT. Interestingly, DHA reduced the expression of GREM1. DHA also inhibited the expression of mesenchymal cell-associated genes and cell migration induced by GREM1. Furthermore, DHA suppressed the expression of p-ERK induced by GREM1. These results indicate that GREM1-ERK axis plays a role in EMT in human breast cancer cells and DHA is a putative compound that can inhibit EMT by inhibiting GREM1 signal transduction.

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Section: Discussionmentioning

confidence: 99%

DHA inhibits Gremlin-1-induced epithelial-to-mesenchymal transition via ERK suppression in human breast cancer cells

et al. 2020

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“…DHA down regulated the expression of VEGF and MMP-9 and upregulated TIMP-1, kisspeptin-1 (KISS-1) and peroxisome proliferator-activated receptor gamma (PPAR-γ) which negatively correlated with cell invasion and metastasis associated gene expression in vitro. DHA restrained the development of sub intestinal vessels and cancer cell metastasis in a zebrafish xenograft model [ 219 ]. In other cell lines, SKOV3 treated with anti-inflammatory and anti-carcinogenic Bisdemethoxycurcumin (BDMC) was shown to inhibit MMP-2, MMP-9 and uPA expression but increase protein expression of TIMP-1 and reduced generation of cellular superoxide in a dose-dependent manner [ 220 ].…”

Section: Metzincins and Timps In Ovarian Cancermentioning

confidence: 99%

The Many Facets of Metzincins and Their Endogenous Inhibitors: Perspectives on Ovarian Cancer Progression

Escalona

Chan

Kannourakis

et al. 2018

IJMS

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Approximately sixty per cent of ovarian cancer patients die within the first five years of diagnosis due to recurrence associated with chemoresistance. The metzincin family of metalloproteinases is enzymes involved in matrix remodeling in response to normal physiological changes and diseased states. Recently, there has been a mounting awareness of these proteinases and their endogenous inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), as superb modulators of cellular communication and signaling regulating key biological processes in cancer progression. This review investigates the role of metzincins and their inhibitors in ovarian cancer. We propose that understanding the metzincins and TIMP biology in ovarian cancer may provide valuable insights in combating ovarian cancer progression and chemoresistance-mediated recurrence in patients.

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“…It is revealed that the LysoPCs might relate with the carcinogenesis and progression of PDAC. The long chain dietary polyunsaturated fatty acid have been found to enhance various cellular responses that reduce cancer cell viability and decrease proliferation both in vitro and in vivo [49][50][51]. A decrease in docosahexaenoic acid indicates a disorder of fatty acids.…”

Section: Discussionmentioning

confidence: 99%

Novel Metabolomics Serum Biomarkers for Pancreatic Ductal Adenocarcinoma by the Comparison of Pre-, Postoperative and Normal Samples

Zhang¹,

Shi²,

Li³

et al. 2020

J. Cancer

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Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human malignancies. The metabolomic approaches are developed to discover the novel biomarkers of PDAC. Methods: 550 preoperative, postoperative PDAC and normal controls (NCs) serums were employed to characterize metabolic alterations in training and validation sets by LC-MS. Results: The results of PLS-DA analysis indicated that three groups could be distinguished clearly and the post-PDAC group is adjacent to a normal group as compared with pre-PDAC group. Further results showed that histidinyl-lysine significantly increased whereas docosahexaenoic acid and LysoPC (14:0) decreased in pre-PDAC patients as compared with NCs. And these three markers had a significant tendency to recover after tumor resection. The validation set results revealed that for CA19-9 negative patients, 92.3% (12/13) of them can be screened using these three metabolites. The combination of these markers could significantly improve the diagnostic performance for PDAC, with higher sensitivity (0.93), specificity (0.92) and AUC (0.97). Moreover, network and pathways analyses explored the latent relationship among differential metabolites. The glycerolipid metabolism and primary bile acid synthesis showed variation in network and pathway analysis. Conclusions: These three markers combined with CA199 displayed high sensitivity and specificity for detecting PDAC patients from NCs. The results indicated that these three metabolites could be regarded as potential biomarkers to distinguish PDAC from NCs.

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Docosahexaenoic Acid Modulates Invasion and Metastasis of Human Ovarian Cancer via Multiple Molecular Pathways

Cited by 16 publications

References 32 publications

DHA inhibits Gremlin-1-induced epithelial-to-mesenchymal transition via ERK suppression in human breast cancer cells

DHA inhibits Gremlin-1-induced epithelial-to-mesenchymal transition via ERK suppression in human breast cancer cells

The Many Facets of Metzincins and Their Endogenous Inhibitors: Perspectives on Ovarian Cancer Progression

Novel Metabolomics Serum Biomarkers for Pancreatic Ductal Adenocarcinoma by the Comparison of Pre-, Postoperative and Normal Samples

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