Suppression of TRPM7 enhances TRAIL‐induced apoptosis in triple‐negative breast cancer cells

Song, Chi-Man; Choi, Seunghye; Oh, Ki Bong; Sim, Taebo

doi:10.1002/jcp.29820

Cited by 21 publications

(11 citation statements)

References 45 publications

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“…Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in various types of cancer cells. Song et al [ 124 ] investigated whether TRPM7 knockdown or pharmacological inhibition of the channel can enhance TRAIL-induced apoptosis in triple-negative breast cancer cells (MDA-MB-231 and MDA-MB-468). Among other findings, the authors demonstrated that pharmacological inhibition of the channel or kinase units in TRPM7 using NS8593 and TG100-115, respectively, synergistically increases TRAIL-induced apoptosis in breast cancer cells [ 124 ].…”

Section: Ns8593 As a Tool To Investigate The Function Of Trpm7 Curmentioning

confidence: 99%

Mapping TRPM7 Function by NS8593

Chubanov¹,

Gudermann²

2020

IJMS

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The transient receptor potential cation channel, subfamily M, member 7 (TRPM7) is a ubiquitously expressed membrane protein, which forms a channel linked to a cytosolic protein kinase. Genetic inactivation of TRPM7 in animal models uncovered the critical role of TRPM7 in early embryonic development, immune responses, and the organismal balance of Zn2+, Mg2+, and Ca2+. TRPM7 emerged as a new therapeutic target because malfunctions of TRPM7 have been associated with anoxic neuronal death, tissue fibrosis, tumour progression, and giant platelet disorder. Recently, several laboratories have identified pharmacological compounds allowing to modulate either channel or kinase activity of TRPM7. Among other small molecules, NS8593 has been defined as a potent negative gating regulator of the TRPM7 channel. Consequently, several groups applied NS8593 to investigate cellular pathways regulated by TRPM7. Here, we summarize the progress in this research area. In particular, two notable milestones have been reached in the assessment of TRPM7 druggability. Firstly, several laboratories demonstrated that NS8593 treatment reliably mirrors prominent phenotypes of cells manipulated by genetic inactivation of TRPM7. Secondly, it has been shown that NS8593 allows us to probe the therapeutic potential of TRPM7 in animal models of human diseases. Collectively, these studies employing NS8593 may serve as a blueprint for the preclinical assessment of TRPM7-targeting drugs.

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Section: Ns8593 As a Tool To Investigate The Function Of Trpm7 Curmentioning

confidence: 99%

Mapping TRPM7 Function by NS8593

Chubanov¹,

Gudermann²

2020

IJMS

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“…Several studies have illustrated the role of glutamate receptor in the pathophysiology mechanisms underlying multiple cancers, including breast cancer, glioblastoma, squamous cell lung cancer, prostate cancer, bladder cancer and melanoma [30][31][32][33][34][35]. Besides, researches have demonstrated the critical role of cation channels in the progression of various type of cancer, especially transient receptor potential cation channel subfamily V member 4 (TRPV4) [36-38], transient receptor potential cation channel subfamily M member 7/8 (TRPM7/8) [39][40][41][42] and two-pore channel 2 (TPC2) [43,44]. TPC2 is one of the cation channels located on endolysosomal membranes that could speed up movement between organelles and regulate phagocytosis, autophagy and lysosomal exocytosis [43].…”

Section: Discussionmentioning

confidence: 99%

“…Another nonselective cation channel TRPM7 involved in Ca 2+ and Mg 2+ homeostasis mainteinance has been found to manage cell differentiation, proliferation and migration. TRPM7 suppression in triple-negative breast cancer (TNBC) cells could amplify tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced antiproliferation and apoptosis [42]. In PAAD, TRPM7 was higher expressed in tumor tissues compared to the normal and correlated to poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value and Immune Infiltration of ARMC10 in Pancreatic Adenocarcinoma Via Integrated Bioinformatics Analyses

Qin

Cheng

et al. 2021

Preprint

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Background: Armadillo repeat-containing 10 (ARMC10) is involved in the progression of multiple types of tumors. Pancreatic adenocarcinoma (PAAD) is a lethal disease with poor survival and prognosis.Methods: We acquired the data of ARMC10 in PAAD patients from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) datasets and compared the expression level with normal pancreatic tissues. We evaluated the relevance between ARMC10 expression and clinicopathological factors, immune infiltration degree and prognosis in PAAD.Results: High expression of ARMC10 was relevant to T stage, M stage, pathologic stage, histologic grade, residual tumor, primary therapy outcome (P<0.05) and related to lower Overall-Survival (OS), Disease-Specific Survival (DSS), and Progression-Free Interval (PFI). Gene set enrichment analysis showed that ARMC10 was related to methylation in neural precursor cells (NPC), G alpha (i) signaling events, APC targets, energy metabolism, potassium channels and IL10 synthesis. The expression level of ARMC10 was positively related to the abundance of T helper cells and negatively to that of plasmacytoid dendritic cells (pDCs). Knocking down of ARMC10 could lead to lower proliferation, invasion, migration ability and colony formation rate of PAAD cells in vitro.Conclusions: Our research firstly discovered ARMC10 as a novel prognostic biomarker for PAAD patients and played a crucial role in immune regulation in PAAD.

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“…More recently, in other breast cancer cells, MDA-MB-231, inhibition of the channel with NS8593, increases the apoptotic and antiproliferative effects induced by TRAIL, while inhibition of kinase activity with TG100-115 has no effect, suggesting that TRPM7 mediates TRAIL-induced apoptosis via calcium ion fluxes [ 109 ]. In addition, downregulation of the activities of the TRPM7 channel could regulate a reduction in the level of c-FLIP L protein promoting the activation of caspase-8, improving apoptosis and decreasing the expression of c-FLIP S .…”

Section: Role Of Trpm7 In Breast Cancer Pathophysiologymentioning

confidence: 99%

TRPM7 Ion Channel: Oncogenic Roles and Therapeutic Potential in Breast Cancer

Cordier

Prevarskaya

Lehen’kyi

2021

Cancers

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The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a divalent cations permeant channel but also has intrinsic serine/threonine kinase activity. It is ubiquitously expressed in normal tissues and studies have indicated that it participates in important physiological and pharmacological processes through its channel-kinase activity, such as calcium/magnesium homeostasis, phosphorylation of proteins involved in embryogenesis or the cellular process. Accumulating evidence has shown that TRPM7 is overexpressed in human pathologies including breast cancer. Breast cancer is the second leading cause of cancer death in women with an incidence rate increase of around 0.5% per year since 2004. The overexpression of TRPM7 may be associated with a poor prognosis in breast cancer patients, so more efforts are needed to research a new therapeutic target. TRPM7 regulates the levels of Ca2+, which can alter the signaling pathways involved in survival, cell cycle progression, proliferation, growth, migration, invasion, epithelial-mesenchymal transition and thus determines cell behavior, promoting tumor development. This work provides a complete overview of the TRPM7 ion channel and its main involvements in breast cancer. Special consideration is given to the modulation of the channel as a potential target in breast cancer treatment by inhibition of proliferation, migration and invasion. Taken together, these data suggest the potential exploitation of TRPM7 channel-kinase as a therapeutic target and a diagnostic biomarker.

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Suppression of TRPM7 enhances TRAIL‐induced apoptosis in triple‐negative breast cancer cells

Cited by 21 publications

References 45 publications

Mapping TRPM7 Function by NS8593

Mapping TRPM7 Function by NS8593

Prognostic Value and Immune Infiltration of ARMC10 in Pancreatic Adenocarcinoma Via Integrated Bioinformatics Analyses

TRPM7 Ion Channel: Oncogenic Roles and Therapeutic Potential in Breast Cancer

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