Tunicamycin-induced endoplasmic reticulum stress reduces in vitro subpopulation and invasion of CD44+/CD24- phenotype breast cancer stem cells

Nami, Babak; Donmez, Huseyin; Koçak, Nadir

doi:10.1016/j.etp.2016.06.004

Cited by 43 publications

(37 citation statements)

References 40 publications

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“…One potential challenge will be the development of agents that specifically target the cyto-protective functions of the UPR ER while either potentiating or maintaining the pro-apoptotic functions of this response. Promising agents [95, 125–136] are under investigation in various types of cancer, and possible combination therapies utilizing ER stress-inducing agents are encouraging approaches (Table 1). In conclusion, UPR ER -mediated induction of the mitochondrial intrinsic apoptosis pathway in response to anticancer targeting is an attractive strategy for novel cancer therapy investigations and thus offers considerable potential for future drug design for the treatment of various malignancies.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Endoplasmic reticulum-mediated unfolded protein response and mitochondrial apoptosis in cancer

Bhat

Chaudhary

Kumar

et al. 2017

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

108

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Abrogation of endoplasmic reticulum (ER) protein folding triggered by exogenous or endogenous factors, stimulates a cellular stress response, termed ER stress. ER stress reestablishes ER homeostasis through integrated signaling termed the ER-unfolded protein response (UPRER). In the presence of severe toxic or prolonged ER stress, the pro-survival function of UPRER is transformed into a lethal signal transmitted to and executed through mitochondria. Mitochondria are key for both apoptotic and autophagic cell death. Thus ER is vital in sensing and coordinating stress pathways to maintain overall physiological homeostasis. However, this function is deregulated in cancer, resulting in resistance to apoptosis induction in response to various stressors including therapeutic agents. Here we review the connections between ER stress and mitochondrial apoptosis, describing potential cancer therapeutic targets.

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Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Endoplasmic reticulum-mediated unfolded protein response and mitochondrial apoptosis in cancer

Bhat

Chaudhary

Kumar

et al. 2017

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

108

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“…The majority of tumor cells derived from metastatic sites of BC patients were highly enriched for a CD44+/CD24− subpopulation [35,36,37]. While CD44+/CD24− cells may be sensitive to some inhibitors [38,39], they often drive tumor resistance to traditional therapies [10]. Studies with tumor tissues from the BC patients who had already received chemotherapy revealed an increased percentage of mammosphere-forming cells with CD44+/CD24− phenotype subpopulation [40].…”

Section: Cd44 Cd24 and Aldh Are The Bc Stemness Markersmentioning

confidence: 99%

HER2 in Breast Cancer Stemness: A Negative Feedback Loop towards Trastuzumab Resistance

Nami

Wang

2017

Cancers

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HER2 receptor tyrosine kinase that is overexpressed in approximately 20% of all breast cancers (BCs) is a poor prognosis factor and a precious target for BC therapy. Trastuzumab is approved by FDA to specifically target HER2 for treating HER2+ BC. However, about 60% of patients with HER2+ breast tumor develop de novo resistance to trastuzumab, partially due to the loss of expression of HER2 extracellular domain on their tumor cells. This is due to shedding/cleavage of HER2 by metalloproteinases (ADAMs and MMPs). HER2 shedding results in the accumulation of intracellular carboxyl-terminal HER2 (p95HER2), which is a common phenomenon in trastuzumab-resistant tumors and is suggested as a predictive marker for trastuzumab resistance. Up-regulation of the metalloproteinases is a poor prognosis factor and is commonly seen in mesenchymal-like cancer stem cells that are risen during epithelial to mesenchymal transition (EMT) of tumor cells. HER2 cleavage during EMT can explain why secondary metastatic tumors with high percentage of mesenchymal-like cancer stem cells are mostly resistant to trastuzumab but still sensitive to lapatinib. Importantly, many studies report HER2 interaction with oncogenic/stemness signaling pathways including TGF-β/Smad, Wnt/β-catenin, Notch, JAK/STAT and Hedgehog. HER2 overexpression promotes EMT and the emergence of cancer stem cell properties in BC. Increased expression and activation of metalloproteinases during EMT leads to proteolytic cleavage and shedding of HER2 receptor, which downregulates HER2 extracellular domain and eventually increases trastuzumab resistance. Here, we review the hypothesis that a negative feedback loop between HER2 and stemness signaling drives resistance of BC to trastuzumab.

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“…Endoplasmic stress has a critical role in regulating cell death. 26 Our results clearly indicated that increased calcium levels in the cytoplasm of PEO-1 cells by either extracellular or intracellular stores was essential for the binding of these cells to fibronectin. Increasing intracellular calcium in PEO-1 cells reduced cell adhesiveness and also PKB/Akt is a serine/threonine kinase that has an important role in cell survival, cell proliferation, invasion, and adhesion to the ECM in various types of cells such as human umbilical vein endothelial cells 27 , breast cancer cell 28 , and lung adenocarcinoma.…”

Section: Discussionmentioning

confidence: 54%

The Ca2+ mobilisation and the inhibition of akt reduced the binding of PEO-1 cells to fibronectin

Kılıçaslan

Ayrim

Apaydın

et al. 2018

tjps

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Tunicamycin-induced endoplasmic reticulum stress reduces in vitro subpopulation and invasion of CD44+/CD24- phenotype breast cancer stem cells

Cited by 43 publications

References 40 publications

Endoplasmic reticulum-mediated unfolded protein response and mitochondrial apoptosis in cancer

Endoplasmic reticulum-mediated unfolded protein response and mitochondrial apoptosis in cancer

HER2 in Breast Cancer Stemness: A Negative Feedback Loop towards Trastuzumab Resistance

The Ca2+ mobilisation and the inhibition of akt reduced the binding of PEO-1 cells to fibronectin

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