Breast Cancer Targeting through Inhibition of the Endoplasmic Reticulum-Based Apoptosis Regulator Nrh/BCL2L10

Nougarède, Adrien; Popgeorgiev, Nikolay; Kassem, Loay; Omarjee, Soleilmane; Borel, Stéphane; Mikaélian, Ivan; Lopez, Jonathan; Gadet, Rudy; Marcillat, Olivier; Treilleux, Isabelle; Villoutreix, Bruno O.; Rimokh, Ruth; Gillet, Germain

doi:10.1158/0008-5472.can-17-0846

Cited by 35 publications

(40 citation statements)

References 42 publications

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“…BQLN1 has been found to specifically interact and stabilize BCLb/BCL2L10, one of the six members of the anti-apoptotic BCL2 family, via the first two of STI domains in the middle of UBQLN1 [44]. Normally, BCLb/BCL2L10 is localized in the mitochondrial and ER membranes and it is degraded in the cytoplasm by UPS [45][46][47]. Upon stimulation of UBQLN1 expression, BCLb/BCL2L10 is relocated into the cytoplasm, ubiquitinated at multiple lysine residues and stabilized, increasing a chance of tumorigenesis and progression [46].…”

Section: Ubqlns and Bcl2 Family Proteinsmentioning

confidence: 99%

Ubiquilin Networking in Cancers

Jantrapirom

Piccolo

Pruksakorn

et al. 2020

Cancers

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Ubiquilins or UBQLNs, members of the ubiquitin-like and ubiquitin-associated domain (UBL-UBA) protein family, serve as adaptors to coordinate the degradation of specific substrates via both proteasome and autophagy pathways. The UBQLN substrates reveal great diversity and impact a wide range of cellular functions. For decades, researchers have been attempting to uncover a puzzle and understand the role of UBQLNs in human cancers, particularly in the modulation of oncogene’s stability and nucleotide excision repair. In this review, we summarize the UBQLNs’ genetic variants that are associated with the most common cancers and also discuss their reliability as a prognostic marker. Moreover, we provide an overview of the UBQLNs networks that are relevant to cancers in different ways, including cell cycle, apoptosis, epithelial-mesenchymal transition, DNA repairs and miRNAs. Finally, we include a future prospective on novel ubiquilin-based cancer therapies.

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Section: Ubqlns and Bcl2 Family Proteinsmentioning

confidence: 99%

Ubiquilin Networking in Cancers

Jantrapirom

Piccolo

Pruksakorn

et al. 2020

Cancers

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“…Other line of research is using small molecules compounds that modify the unbalance Ca 2+ homeostasis in cancer cells. For example, the Nhr-BH4, a BCL-2 mimetic peptide that prevents the inhibition of the IP 3 R Ca 2+ release and thus unblock the apoptosis resistance in breast cancer cells (Nougarede et al, 2018). The TAT-IDPs, other BCL-2 based peptide, potentiates the pro-apoptotic Ca 2+ signaling in chronic lymphocytic leukemia cells avoiding the IP 3 R 2 inhibition, an IP 3 R homolog, (Akl et al, 2013).…”

Section: Crac Channel Modulators and Cancermentioning

confidence: 99%

Calcium Permeable Channels in Cancer Hallmarks

Tajada¹,

Villalobos²

2020

Front. Pharmacol.

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Cancer, the second cause of death worldwide, is characterized by several common criteria, known as the "cancer hallmarks" such as unrestrained cell proliferation, cell death resistance, angiogenesis, invasion and metastasis. Calcium permeable channels are proteins present in external and internal biological membranes, diffusing Ca 2+ ions down their electrochemical gradient. Numerous physiological functions are mediated by calcium channels, ranging from intracellular calcium homeostasis to sensory transduction. Consequently, calcium channels play important roles in human physiology and it is not a surprise the increasing number of evidences connecting calcium channels disorders with tumor cells growth, survival and migration. Multiple studies suggest that calcium signals are augmented in various cancer cell types, contributing to cancer hallmarks. This review focuses in the role of calcium permeable channels signaling in cancer with special attention to the mechanisms behind the remodeling of the calcium signals. Transient Receptor Potential (TRP) channels and Store Operated Channels (SOC) are the main extracellular Ca 2+ source in the plasma membrane of nonexcitable cells, while inositol trisphosphate receptors (IP 3 R) are the main channels releasing Ca 2+ from the endoplasmic reticulum (ER). Alterations in the function and/or expression of these calcium channels, as wells as, the calcium buffering by mitochondria affect intracellular calcium homeostasis and signaling, contributing to the transformation of normal cells into their tumor counterparts. Several compounds reported to counteract several cancer hallmarks also modulate the activity and/or the expression of these channels including non-steroidal anti-inflammatory drugs (NSAIDs) like sulindac and aspirin, and inhibitors of polyamine biosynthesis, like difluoromethylornithine (DFMO). The possible role of the calcium permeable channels targeted by these compounds in cancer and their action mechanism will be discussed also in the review.

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“…In fact, Nrh may indirectly prevent apoptosis by controlling ER-stress. Indeed, there is evidence that Nrh acts upstream of the Unfolded Protein Response (UPR) by inhibiting ERCa 2+ release through IP3R closure (Nougarede et al, 2018 ).…”

Section: Moonlighting Functions Of the Bcl-2 Proteins In Respect To Tmentioning

confidence: 99%

Subcellular Localization and Dynamics of the Bcl-2 Family of Proteins

Popgeorgiev

Jabbour

Gillet

2018

Front. Cell Dev. Biol.

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160

121

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Bcl-2 family proteins are recognized as major regulators of the mitochondrial pathway of apoptosis. They control the mitochondrial outer membrane permeabilization (MOMP) by directly localizing to this organelle. Further investigations demonstrated that Bcl-2 related proteins are also found in other intracellular compartments such as the endoplasmic reticulum, the Golgi apparatus, the nucleus and the peroxisomes. At the level of these organelles, Bcl-2 family proteins not only regulate MOMP in a remote fashion but also participate in major cellular processes including calcium homeostasis, cell cycle control and cell migration. With the advances of live cell imaging techniques and the generation of fluorescent recombinant proteins, it became clear that the distribution of Bcl-2 proteins inside the cell is a dynamic process which is profoundly affected by changes in the cellular microenvironment. Here, we describe the current knowledge related to the subcellular distribution of the Bcl-2 family of proteins and further emphasize on the emerging concept that this highly dynamic process is critical for cell fate determination.

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Breast Cancer Targeting through Inhibition of the Endoplasmic Reticulum-Based Apoptosis Regulator Nrh/BCL2L10

Cited by 35 publications

References 42 publications

Ubiquilin Networking in Cancers

Ubiquilin Networking in Cancers

Calcium Permeable Channels in Cancer Hallmarks

Subcellular Localization and Dynamics of the Bcl-2 Family of Proteins

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