Role of TRPM7 in Cancer: Potential as Molecular Biomarker and Therapeutic Target

Yee, Nelson S.

doi:10.3390/ph10020039

Cited by 72 publications

(69 citation statements)

References 82 publications

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“…Nevertheless, taking into account the MI and the tumour location, the CFA 30 amplification was not any more significant, probably because of its strong association with the MI. Indeed, genes lying on this recurrent amplified region probably bring an advantage for the proliferation and progression of the tumour, such as TRPM7 involved in the MAPK pathway . Focal amplifications along CFA 10 were often found in two distinct regions covering the targeted genes MDM2 and the cycline‐dependent‐kinase CDK4 , and this association was demonstrated in a previous study .…”

Section: Discussionsupporting

confidence: 51%

Prognostic value of somatic focal amplifications on chromosome 30 in canine oral melanoma

Prouteau

Chocteau

Brito

et al. 2019

Vet Comparative Oncology

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Canine oral melanoma is the first malignancy of the oral cavity in dogs and is characterized by a local invasiveness and a high metastatic propensity. A better knowledge of genetic alterations is expected to improve management of this tumour. Copy number alterations are known characteristics of mucosal melanomas both in dogs and humans. The goal of this study was to explore the prognostic value of somatic focal amplifications on chromosomes (Canis Familiaris [CFA]) 10 and 30 in canine oral melanoma. The cohort included 73 dogs with oral melanoma confirmed by histology, removed surgically without adjuvant therapy and with a minimal follow-up of 6 months. Epidemiological, clinical and histological data were collected and quantitative-PCR were performed on formalin-fixed paraffin-embedded (FFPE) samples to identify specific focal amplifications. The 73 dogs included in the study had a median survival time of 220 days. Focal amplifications on CFA 10 and 30 were recurrent (49.3% and 50.7% of cases, respectively) and CFA 30 amplification was significantly associated with the amelanotic phenotype (P = .046) and high mitotic index (MI; P = .0039). CFA 30 amplification was also linked to poor prognosis (P = .0005). Other negative prognostic factors included gingiva location (P = .003), lymphadenomegaly (P = .026), tumour ulceration at diagnosis (P = .003), MI superior to 6 mitoses over 10 fields (P = .001) and amelanotic tumour (P = .029). In multivariate analyses using Cox proportional hazards regression, CFA 30 amplification (Hazard ratio [HR] = 2.08; P = .011), tumour location (HR = 2.20; P = .005) and histological pigmentation (HR = 1.87; P = .036) were significantly associated with shorter survival time. Focal amplification of CFA 30 is linked to an aggressive subset and constitutes a new prognostic factor.

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Section: Discussionsupporting

confidence: 51%

Prognostic value of somatic focal amplifications on chromosome 30 in canine oral melanoma

Prouteau

Chocteau

Brito

et al. 2019

Vet Comparative Oncology

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“…In as much as the mechanism of TRPM7 regulation of the cell cycle is still unclear and may involve some cell cycle checkpoint signaling [40], we found that the channel function of TRPM7 promotes the activity of cells in the G1 and S phases. This is in agreement with a previous finding that the Ca 2+ and Mg 2+ influx mediated by TRPM7 channels improves the activities of cells in the S phase [8,41].…”

Section: Discussionsupporting

confidence: 94%

“…There is a tendency for worse outcomes when the TRPM7 gene is highly expressed ( Figure S3). TRPM7 is found to be more highly expressed in some types of human cancer tissue compared to adjacent non-tumor tissue [24] and is thought to be associated with cancer development [8]. The effect of TRPM7 is complex because it affects cells both by regulating the flux of divalent cations into the cell and by regulating intracellular processes via the enzymatic activity of the kinase domain in its C-terminal region [25].…”

Section: Discussionmentioning

confidence: 99%

“…There are six subfamilies in the TRP superfamily of ion channels and one of them, the melastatin-like transient receptor potential (TRPM), has eight members, TRPM1 to TRPM8 [4][5][6]. The data suggest that TRPM7 (also known as LTRPC7, ChaK1 and TRP-PLIK) is aberrantly expressed in cancer cells and plays a crucial role in cancer [7], implying a role for TRPM7 as a molecular biomarker and a therapeutic target in human malignancies [8].…”

Section: Introductionmentioning

confidence: 99%

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The Role of Transient Receptor Potential Melastatin 7 (TRPM7) in Cell Viability: A Potential Target to Suppress Breast Cancer Cell Cycle

Liu

Dilger

Lin

2020

Cancers

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The divalent cation-selective channel transient receptor potential melastatin 7 (TRPM7) channel was shown to affect the proliferation of some types of cancer cell. However, the function of TRPM7 in the viability of breast cancer cells remains unclear. Here we show that TRPM inhibitors suppressed the viability of TRPM7-expressing breast cancer cells. We first demonstrated that the TRPM7 inhibitors 2-aminoethyl diphenylborinate (2-APB), ginsenoside Rd (Gin Rd), and waixenicin A preferentially suppressed the viability of human embryonic kidney HEK293 overexpressing TRPM7 (HEK-M7) cells over wildtype HEK293 (WT-HEK). Next, we confirmed the effects of 2-APB on the TRPM7 channel functions by whole-cell currents and divalent cation influx. The inhibition of the viability of HEK-M7 cells by 2-APB was not mediated by the increase in cell death but by the interruption of the cell cycle. Similar to HEK-M7 cells, the viability of TRPM7-expressing human breast cancer MDA-MB-231, AU565, and T47D cells were also suppressed by 2-APB by arresting the cell cycle in the S phase. Furthermore, in a novel TRPM7 knock-out MDA-MB-231 (KO-231) cell line, decreased divalent influx and reduced proliferation were observed compared to the wildtype MDA-MB-231 cells. 2-APB and Gin Rd preferentially suppressed the viability of wildtype MDA-MB-231 cells over KO-231 by affecting the cell cycle in wildtype but not KO-231 cells. Our results suggest that TRPM7 regulates the cell cycle of breast cancers and is a potential therapeutic target.

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“…Transient receptor potential melastatin 7 (TRPM7) is a ubiquitously expressed ion channel with intrinsic kinase activity (5). Review studies have indicated the important roles of TRPM7 channel kinase in fundamental cellular processes, physiologic responses, and embryonic development (5,6). Accumulating evidence has shown that TRPM7 is aberrantly expressed and/ or activated in human diseases including cancer, and plays a variety of functional roles in cancer cells including survival, cell-cycle progression, proliferation, growth, migration, invasion, and epithelial-mesenchymal transition (5,6).…”

Section: Introductionmentioning

confidence: 99%

TRPM7 Regulates AKT/FOXO1–Dependent Tumor Growth and Is an Independent Prognostic Indicator in Renal Cell Carcinoma

Zhao

Zhang

Duan

et al. 2018

Molecular Cancer Research

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Transient receptor potential melastatin 7 (TRPM7) is important for the tumorigenesis and progression of several cancers. However, little is known about TRPM7 expression and its clinical significance in clear cell renal cell carcinoma (ccRCC). The expression dynamics of TRPM7 was examined in a clinical cohort of RCC specimens by qPCR, immunoblotting, and IHC staining. A series of and assays were performed to elucidate the function of TRPM7 in RCC and the underlying mechanisms. For the first time, results demonstrate that TRPM7 expression is markedly higher in RCC cell lines and clinical samples and had a positive correlation with T status, tumor size, and poor patients' overall survival and progression-free survival. Preclinical studies using multiple RCC cells and a mouse model indicate that TRPM7 promotes cell proliferation and colony formation and tumor growth Mechanistically, TRPM7 promotes AKT phosphorylation, leading to repression of the FOXO1 expression and transcriptional activity. Moreover, luciferase reporter assays demonstrate that miR-129-3p directly targets the 3'-UTR of TRPM7 and acts as a negative regulator of TRPM7. These findings reveal an important role for TRPM7 in the regulation of RCC growth and represent a novel prognostic biomarker for this disease. TRPM7 is an independent prognostic indicator in RCC, and targeting the TRPM7 signaling pathway may be a novel therapeutic approach for the treatment of RCC. .

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Role of TRPM7 in Cancer: Potential as Molecular Biomarker and Therapeutic Target

Cited by 72 publications

References 82 publications

Prognostic value of somatic focal amplifications on chromosome 30 in canine oral melanoma

Prognostic value of somatic focal amplifications on chromosome 30 in canine oral melanoma

The Role of Transient Receptor Potential Melastatin 7 (TRPM7) in Cell Viability: A Potential Target to Suppress Breast Cancer Cell Cycle

TRPM7 Regulates AKT/FOXO1–Dependent Tumor Growth and Is an Independent Prognostic Indicator in Renal Cell Carcinoma

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