Tumor suppressor candidate 3 (TUSC3) prevents the epithelial-to-mesenchymal transition and inhibits tumor growth by modulating the endoplasmic reticulum stress response in ovarian cancer cells

In this paper, we investigate whether Wnt5A is associated with the TGF-β1/Smad2/3 and Hippo-YAP1/TAZ-TEAD pathways, implicated in epithelial to mesenchymal transition (EMT) in epithelial ovarian cancer. We used 3D and 2D cultures of human epithelial ovarian cancer cell lines SKOV-3, OVCAR-3, CAOV-4, and different subtypes of human serous ovarian cancer compared to normal ovary specimens. Wnt5A showed a positive correlation with TAZ and TGFβ1 in high- and low-grade serous ovarian cancer specimens compared to borderline serous and normal ovaries. Silencing Wnt5A by siRNAs significantly decreased Smad2/3 activation and YAP1 expression and nuclear shuttling in ovarian cancer (OvCa) cells. Furthermore, Wnt5A was required for TGFβ1-induced cell migration and invasion. In addition, inhibition of YAP1 transcriptional activity by Verteporfin (VP) altered OvCa cell migration and invasion through decreased Wnt5A expression and inhibition of Smad2/3 activation, which was reverted in the presence of exogenous Wnt5A. We found that the activation of TGFβ1 and YAP1 nuclear shuttling was promoted by Wnt5A-induced integrin alpha v. Lastly, Wnt5A was implicated in activating human primary omental mesothelial cells and subsequent invasion of ovarian cancer cells. Together, we propose that Wnt5A could be a critical mediator of EMT-associated pathways.

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CBIO-29. ACOT7 REGULATES COLONIZATION OF BREAST CANCER CELLS IN THE BRAIN BY REGULATING ENDOPLASMIC RETICULUM STRESS RESPONSE

Neuro-Oncology ◽

10.1093/neuonc/nox168.147 ◽

2017 ◽

Vol 19 (suppl_6) ◽

pp. vi38-vi38

Author(s):

Deepak Kanojia ◽

Wojciech K Panek ◽

Alex Cordero ◽

Annie Xiao ◽

Jason Miska ◽

...

Keyword(s):

Breast Cancer ◽

Endoplasmic Reticulum ◽

Stress Response ◽

Endoplasmic Reticulum Stress ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Endoplasmic Reticulum Stress Response ◽

The Brain

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Fucosterol Suppresses the Progression of Human Ovarian Cancer by Inducing Mitochondrial Dysfunction and Endoplasmic Reticulum Stress

Marine Drugs ◽

10.3390/md18050261 ◽

2020 ◽

Vol 18 (5) ◽

pp. 261 ◽

Cited By ~ 1

Author(s):

Hyocheol Bae ◽

Jin-Young Lee ◽

Gwonhwa Song ◽

Whasun Lim

Keyword(s):

Ovarian Cancer ◽

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Cancer Cells ◽

Cell Cycle Progression ◽

Xenograft Model ◽

Tumor Formation ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Anticancer Properties

Ovarian cancer is difficult to diagnose early and has high rates of relapse and mortality. Therefore, the treatment of ovarian cancer needs to be improved. Recently, several studies have been conducted in an attempt to develop anticancer drugs from naturally derived ingredients. Compared to traditional chemotherapy, natural compounds can overcome drug resistance with lower side effects. Fucosterol, a phytosterol present in brown algae, reportedly possesses many bioactive effects, including anticancer properties. However, the anticancer effects of fucosterol in ovarian cancer remain unexplored. Therefore, we investigated the effects of fucosterol on progression in human ovarian cancer cells. Fucosterol inhibited cell proliferation and cell-cycle progression in ovarian cancer cells. Additionally, fucosterol regulated the proliferation-related signaling pathways, the production of reactive oxygen species, mitochondrial function, endoplasmic reticulum stress, angiogenesis, and calcium homeostasis. Moreover, it decreased tumor formation in a zebrafish xenograft model. These results indicate that fucosterol could be used as a potential therapeutic agent in ovarian cancer.

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