Identification of TG100-115 as a new and potent TRPM7 kinase inhibitor, which suppresses breast cancer cell migration and invasion

Song, Chi-Man; Bae, Yeonju; Jun, Jin Joo; Lee, Hyomin; Kim, Nam Doo; Lee, Kyung Bok; Hur, Wooyoung; Park, Jae Yong; Sim, Taebo

doi:10.1016/j.bbagen.2017.01.034

Cited by 48 publications

(38 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also found that TG100-115 efficiently inactivates TRPM6 kinase in living cells [ 21 ]. Besides, Song et al [ 109 ] examined the effects of TG100-115 on the TRPM7 kinase and reported that this reagent inhibits the TRPM7 kinase with an IC 50 of 2 µM. Finally, it is worth mentioning that in our hands, neither NS8593 nor naltriben directly affected the kinase activity of TRPM7 (unpublished observations).…”

Section: Drug-like Modulators the Channel And Kinase Activity Of Tmentioning

confidence: 58%

Mapping TRPM7 Function by NS8593

Chubanov¹,

Gudermann²

2020

IJMS

View full text Add to dashboard Cite

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.

show abstract

Section: Drug-like Modulators the Channel And Kinase Activity Of Tmentioning

confidence: 58%

Mapping TRPM7 Function by NS8593

Chubanov¹,

Gudermann²

2020

IJMS

View full text Add to dashboard Cite

show abstract

“…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). In recent studies, TRPM7 was identified as a regulator of PI3K/Akt, MAPK, and ERK1/2 pathways, regulating several oncogenes regulators and cell-cycle genes, and its function was potentially associated with several human cancers, such as human colon cancer, ovarian cancer, prostate cancer, breast cancer, bladder cancer, pancreatic cancer, nasopharyngeal carcinoma, and esophageal squamous cell carcinoma (7)(8)(9)(10)(11)(12)(13). Up to now, no association of TRPM7 and RCC was reported, and the significance of TRPM7 expression on prognosis in ccRCC has not been elucidated.…”

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

View full text Add to dashboard Cite

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. .

show abstract

“…This inhibitor shows little effect on the proliferation of MDA-MB-231 on BCs, but significantly inhibits the migration and invasion of BC cells as a consequence of reduced myosin IIA heavy chain and focal adhesion kinase (FAK) phosphorylation. TG100-115 also suppressed the TRPM7 channel activity [38].…”

Section: Trpm Channels In Cancer Therapymentioning

confidence: 92%

Transient Receptor Potential Cation Channels in Cancer Therapy

et al. 2019

View full text Add to dashboard Cite

In mammals, the transient receptor potential (TRP) channels family consists of six different families, namely TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPML (mucolipin), TRPP (polycystin), and TRPA (ankyrin), that are strictly connected with cancer cell proliferation, differentiation, cell death, angiogenesis, migration, and invasion. Changes in TRP channels’ expression and function have been found to regulate cell proliferation and resistance or sensitivity of cancer cells to apoptotic-induced cell death, resulting in cancer-promoting effects or resistance to chemotherapy treatments. This review summarizes the data reported so far on the effect of targeting TRP channels in different types of cancer by using multiple TRP-specific agonists, antagonists alone, or in combination with classic chemotherapeutic agents, microRNA specifically targeting the TRP channels, and so forth, and the in vitro and in vivo feasibility evaluated in experimental models and in cancer patients. Considerable efforts have been made to fight cancer cells, and therapies targeting TRP channels seem to be the most promising strategy. However, more in-depth investigations are required to completely understand the role of TRP channels in cancer in order to design new, more specific, and valuable pharmacological tools.

show abstract

Identification of TG100-115 as a new and potent TRPM7 kinase inhibitor, which suppresses breast cancer cell migration and invasion

Cited by 48 publications

References 47 publications

Mapping TRPM7 Function by NS8593

Mapping TRPM7 Function by NS8593

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

Transient Receptor Potential Cation Channels in Cancer Therapy

Contact Info

Product

Resources

About