期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 12, 页码 -出版社
MDPI
DOI: 10.3390/ijms23126672
关键词
prostate cancer; tumor growth; metastasis dissemination; TRPM8; Rho signaling; ERK; FAK; cell proliferation; trans-endothelial migration; invasion
资金
- Ministere de l'Education Nationale
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- region Hauts-de-France
- University of Lille
- Institut Universitaire de France (IUF)
- France Berkley Fund
- Institut National du Cancer [INCa-PLBIO14-213]
- CPER Photonics for Society
- Italian Ministry of Instruction, University and Research (MIUR), PRIN grant Leveraging basic knowledge of ion channel network in cancer for innovative therapeutic strategies (LIONESS) [20174TB8KW]
- Deutsche Forschungsgemeinschaft [SCHW 407/22-1]
TRPM8 plays a protective role in the progression of prostate cancer and may be a potential therapeutic target. The study demonstrated that TRPM8 overexpression can significantly inhibit tumor growth and metastasis in prostate cancer using a mouse model and in vitro experiments.
In the fight against prostate cancer (PCa), TRPM8 is one of the most promising clinical targets. Indeed, several studies have highlighted that TRPM8 involvement is key in PCa progression because of its impact on cell proliferation, viability, and migration. However, data from the literature are somewhat contradictory regarding the precise role of TRPM8 in prostatic carcinogenesis and are mostly based on in vitro studies. The purpose of this study was to clarify the role played by TRPM8 in PCa progression. We used a prostate orthotopic xenograft mouse model to show that TRPM8 overexpression dramatically limited tumor growth and metastasis dissemination in vivo. Mechanistically, our in vitro data revealed that TRPM8 inhibited tumor growth by affecting the cell proliferation and clonogenic properties of PCa cells. Moreover, TRPM8 impacted metastatic dissemination mainly by impairing cytoskeleton dynamics and focal adhesion formation through the inhibition of the Cdc42, Rac1, ERK, and FAK pathways. Lastly, we proved the in vivo efficiency of a new tool based on lipid nanocapsules containing WS12 in limiting the TRPM8-positive cells' dissemination at metastatic sites. Our work strongly supports the protective role of TRPM8 on PCa progression, providing new insights into the potential application of TRPM8 as a therapeutic target in PCa treatment.
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