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Role of TRPM7 in Cancer: Potential as Molecular Biomarker and Therapeutic Target
1Division of Hematology-Oncology, Department of Medicine, PennState Health Milton S. Hershey Medical Center, Program of Experimental Therapeutics, PennState Cancer Institute, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA. nyee@pennstatehealth.psu.edu.
Abstract:
The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a ubiquitously expressed ion channel with intrinsic kinase activity. Molecular and electrophysiological analyses of the structure and activity of TRPM7 have revealed functional coupling of its channel and kinase activity. Studies have indicated the important roles of TRPM7 channel-kinase in fundamental cellular processes, physiological responses, and embryonic development. Accumulating evidence has shown that TRPM7 is aberrantly expressed and/or activated in human diseases including cancer. TRPM7 plays a variety of functional roles in cancer cells including survival, cell cycle progression, proliferation, growth, migration, invasion, and epithelial-mesenchymal transition (EMT). Data from a study using mouse xenograft of human cancer show that TRPM7 is required for tumor growth and metastasis. The aberrant expression of TRPM7 and its genetic mutations/polymorphisms have been identified in various types of carcinoma. Chemical modulators of TRPM7 channel produced inhibition of proliferation, growth, migration, invasion, invadosome formation, and markers of EMT in cancer cells. Taken together, these studies suggest the potential value of exploiting TRPM7 channel-kinase as a molecular biomarker and therapeutic target in human malignancies.
Insights
The transient receptor potential melastatin-subfamily member 7 (TRPM7) channel-kinase is crucial for cancer cell survival and metastasis. Targeting TRPM7 offers a promising therapeutic strategy for human malignancies.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- The transient receptor potential melastatin-subfamily member 7 (TRPM7) is an ion channel with kinase activity.
- TRPM7 plays vital roles in cellular functions, physiological responses, and embryonic development.
- Aberrant TRPM7 expression is linked to human diseases, particularly cancer.
Purpose of the Study:
- To investigate the role of TRPM7 channel-kinase in cancer.
- To explore TRPM7 as a potential therapeutic target and biomarker in malignancies.
Main Methods:
- Molecular and electrophysiological analyses of TRPM7 structure and activity.
- Studies on TRPM7's role in cancer cell survival, proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT).
- Evaluation of TRPM7's requirement for tumor growth and metastasis in mouse xenograft models.
- Analysis of TRPM7 expression and mutations in various carcinomas.
- Assessment of chemical modulators targeting TRPM7 in cancer cells.
Main Results:
- TRPM7 channel-kinase activity is functionally coupled.
- TRPM7 is implicated in key cancer cell processes, including survival, proliferation, migration, invasion, and EMT.
- TRPM7 is essential for tumor growth and metastasis in vivo.
- Aberrant TRPM7 expression and mutations are found in various carcinomas.
- Chemical TRPM7 modulators inhibit cancer cell proliferation, migration, invasion, and EMT markers.
Conclusions:
- TRPM7 channel-kinase plays significant roles in cancer progression.
- TRPM7 is a potential molecular biomarker for human malignancies.
- Targeting TRPM7 presents a promising therapeutic strategy for cancer treatment.