Overcoming Multidrug Resistance by Activating Unfolded Protein Response of the Endoplasmic Reticulum in Cisplatin-Resistant A2780/CisR Ovarian Cancer Cells

There is an ongoing need for development of new therapeutics that override acquired resistance to cancer therapy. Targeting endoplasmic reticulum by Cu(ii)–phenanthroline complexes may represent such alternative strategy to current cytotoxic drugs.

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Linking endoplasmic reticulum stress to polyploidy in ovarian cancer cells

10.1101/2020.01.24.918029 ◽

2020 ◽

Author(s):

Lucile Yart ◽

Daniel Bastida-Ruiz ◽

Christine Wuillemin ◽

Pascale Ribaux ◽

Mathilde Allard ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cell Fusion ◽

Ovarian Cancer Cells ◽

Parental Cancer ◽

Chemical Inducers ◽

Unfolded Protein ◽

Ovarian Cancer Cell Lines ◽

Perk Expression ◽

Protein Response

AbstractPolyploid giant cancer cells (PGCCs) have been observed in epithelial ovarian tumors and have the ability to survive to antimitotic drugs. Their appearance can result from paclitaxel treatment or hypoxia, two conditions known to induce unfolded protein response (UPR) activation. PGCCs produced under hypoxia may be formed by cell fusion and can contribute by bursting and budding to the generation of cancer stem-like cells which have a more aggressive phenotype than the parental cells. Despite the fact that PGCCs may contribute to tumor maintenance and recurrence, they were poorly studied. Here, we confirmed that PGCCs could derive, at least in part, from cell fusion. We also observed that PGCCs nuclei were able to fuse. The resulting cells were able to proliferate by mitosis and were more invasive than the parental cancer cells. Using two different ovarian cancer cell lines (COV318 and SKOV3), we showed that UPR activation with chemical inducers increased cell fusion and PGCCs appearance. Down-regulation of the UPR-associated protein PERK expression partially reversed the UPR-induced PGCCs formation, suggesting that the PERK arm of the UPR is involved in ovarian PGCCs onset.

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Silver nanoparticles induce irremediable endoplasmic reticulum stress leading to unfolded protein response dependent apoptosis in breast cancer cells

APOPTOSIS ◽

10.1007/s10495-016-1285-7 ◽

2016 ◽

Vol 21 (11) ◽

pp. 1279-1290 ◽

Cited By ~ 32

Author(s):

Jean-Christophe Simard ◽

Isabelle Durocher ◽

Denis Girard

Keyword(s):

Breast Cancer ◽

Silver Nanoparticles ◽

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Unfolded Protein Response ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Unfolded Protein ◽

Protein Response

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Knockdown of CEMIP suppresses proliferation and induces apoptosis in colorectal cancer cells: downregulation of GRP78 and attenuation of unfolded protein response

Biochemistry and Cell Biology ◽

10.1139/bcb-2017-0151 ◽

2018 ◽

Vol 96 (3) ◽

pp. 332-341 ◽

Cited By ~ 5

Author(s):

Guodong Liang ◽

Xuedong Fang ◽

Yubo Yang ◽

Yan Song

Keyword(s):

Colorectal Cancer ◽

Endoplasmic Reticulum ◽

Unfolded Protein Response ◽

Cancer Cells ◽

G1 Arrest ◽

Cyclin E1 ◽

Unfolded Protein ◽

Induced Apoptosis ◽

Protein Response

It has been suggested that cell migration inducing hyaluronan binding protein (CEMIP) contributes to the carcinogenesis of colorectal cancer (CRC). Cancer cells can adapt to endoplasmic reticulum (ER) stress by initiating an unfolded protein response (UPR). This study aimed to investigate whether CEMIP affects the UPR of CRC cells, with a focus on 78 kDa glucose-regulated protein (GRP78, a major ER chaperone). We found that knockdown of CEMIP inhibited cell proliferation and induced a G1 arrest in SW480 CRC cells. The levels of cyclin D1 and cyclin E1 and phospho-retinoblastoma, which are known to promote the cell cycle progression from G0 or G1 into S phase, were decreased in CEMIP-silenced cells. CEMIP shRNA induced apoptosis and inhibited GRP78 expression in SW480 and Colo205 cells. The basal UPR of cancer cells was attenuated by CEMIP shRNA, as evidenced by the decreased expression of UPR sensors, protein kinase R-like endoplasmic reticulum kinase (PERK), inositol requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6). Furthermore, CEMIP silencing sensitized CRC cells to thapsigargin-induced apoptosis. Our study demonstrates that the in-vitro anti-proliferative and pro-apoptotic effects in CRC cells that were induced by silencing CEMIP may be associated with GRP78 repression and UPR attenuation.

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