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Published on: December 31, 2013
TRPM channels in human cancers: regulatory mechanism and therapeutic prospects
Qinfeng Liu1, Mengyu Hu1, Shi Li1
1National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan, 430074, China.
Abstract:
The transient receptor potential melastatin (TRPM) channel family has been previously implicated in various diseases, including those related to temperature sensing, cardiovascular health, and neurodegeneration. Nowadays, increasing evidence indicates that TRPM family members also play significant roles in various types of cancers, exhibiting both pro- and anti-tumorigenic functions. They are involved in tumor cell proliferation, survival, invasion, and metastasis, serving as potential diagnostic and prognostic biomarkers for cancer. This paper begins by describing the structure and physiological functions of the TRPM family members. It then outlines their roles in several common malignancies, including pancreatic, prostate, colorectal, breast, brain cancer, and melanoma. Subsequently, we focused on investigating the specific mechanisms by which TRPM family members are involved in tumorigenesis and development from both the tumor microenvironment (TME) and intracellular signaling. TRPM channels not only transmit signals from the TME to regulate tumor cell functions, but also mediate extracellular matrix remodeling, which is conducive to the malignant transformation of tumor cells. Importantly, TRPM channels depend on the regulation of the inflow of various ions in cells, and participate in key signaling pathways involved in tumor progression, such as Wnt/β-catenin, MAPK, PI3K/AKT, p53, and autophagy. Finally, we summarize the current strategies and challenges of targeting TRPM channels in tumor treatment, and discuss the feasibility of combining targeted TRPM channel drugs with cancer immunotherapy.
Insights
Transient Receptor Potential Melastatin (TRPM) channels are increasingly linked to cancer, influencing tumor growth and metastasis. Targeting TRPM channels offers potential new strategies for cancer treatment and immunotherapy.
Area of Science:
- Molecular Biology
- Oncology
- Ion Channel Physiology
Background:
- Transient Receptor Potential Melastatin (TRPM) channels are implicated in diseases, including cancer.
- TRPM channels exhibit both pro- and anti-tumorigenic functions in various malignancies.
- They are involved in tumor cell proliferation, survival, invasion, and metastasis, acting as potential biomarkers.
Purpose of the Study:
- To describe the structure and physiological functions of TRPM channel family members.
- To outline the roles of TRPM channels in common cancers like pancreatic, prostate, colorectal, breast, brain cancer, and melanoma.
- To investigate the mechanisms of TRPM channel involvement in tumorigenesis from the tumor microenvironment and intracellular signaling.
Main Methods:
- Literature review and analysis of existing research on TRPM channels in cancer.
- Examination of TRPM channel involvement in tumor cell functions, including proliferation, survival, invasion, and metastasis.
- Analysis of TRPM channel roles in signaling pathways (Wnt/β-catenin, MAPK, PI3K/AKT, p53, autophagy) and the tumor microenvironment.
Main Results:
- TRPM channels are involved in tumor cell proliferation, survival, invasion, and metastasis.
- They mediate extracellular matrix remodeling, aiding malignant transformation.
- TRPM channels regulate ion inflow and participate in key cancer signaling pathways.
Conclusions:
- TRPM channels are crucial in cancer development and progression.
- Targeting TRPM channels presents therapeutic opportunities and challenges in cancer treatment.
- Combining TRPM channel-targeted drugs with cancer immunotherapy is a promising future direction.
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