IMR Press / JOMH / Volume 18 / Issue 7 / DOI: 10.31083/j.jomh1807144
Open Access Original Research
Inhibition of TRPM7 suppresses migration and invasion of prostate cancer cells via inactivation of ERK1/2, Src and Akt pathway signaling
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1 Joint Institute for Regenerative Medicine, Kyungpook National University, 41571 Daegu, Republic of Korea
2 Department of Urology, School of Medicine, Kyungpook National University, 41571 Daegu, Republic of Korea
3 Department of Urology, School of Medicine, Kyungpook National University Chilgok Hospital, 41944 Daegu, Republic of Korea
4 Department of Brain and Cognitive Sciences, Core Protein Resources Center, Daegu Gyeongbuk Institue of Science and Technology (DGIST), 42988 Daegu, Republic of Korea
5 BioMedical Research Institute, Kyungpook National University Hospital, 41944 Daegu, Republic of Korea
6 Department of Urology, School of Medicine, Kyungpook National University Hospital, 41944 Daegu, Republic of Korea
7 BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, 41571 Daegu, Republic of Korea
8 Department of Urology, Yeungnam University College of Medicine, 42415 Daegu, Republic of Korea
*Correspondence: tgkwon@knu.ac.kr (Tae Gyun Kwon); yunsokha@knu.ac.kr (Yun-Sok Ha)
These authors contributed equally.
J. Mens. Health 2022, 18(7), 144; https://doi.org/10.31083/j.jomh1807144
Submitted: 14 December 2021 | Revised: 7 January 2021 | Accepted: 10 January 2021 | Published: 29 June 2022
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: Prostate cancer is the second most common cause of cancer related death in males worldwide. Most patients show no response to androgen deprivation therapy in case of recurrence and proceed to advanced stage with metastasis. TRPM7 is reported to be upregulated in diverse types of tumors. Methods: We analyzed the expression of TRPM7 and related proteins by Western blotting analysis. We performed cell migration and invasion assay to analyze the relationship between tumor aggressiveness and TRPM7. In addition, we proceeded an animal study by using stable TRPM7 knockdown cell line in xenograft. Results: In our results, TRPM7 regulates prostate cancer cell biology including proliferation, migration and invasion through ERK1/2, PI3K/Akt and JNK signaling pathways. We produced stable TRPM7 knockdown prostate cancer cell line. To analyze the relationship between TRPM7 and tumorigenesis, we proceeded migration and invasion assay as well as xenograft model. TRPM7 down-regulated DU145 cells showed suppressed migratory and invasion ability, 0.65- and 0.05-fold, respectively. In addition, we confirmed that the anti-cancer effect of TRPM7 is mediated through inactivation of ERK1/2, Src and Akt signaling pathways by western blotting analysis. P-ERK1/2, p-Src, and p-Akt expressions were reduced to 0.66-, 0.68-, and 0.66-fold, respectively. Moreover, we treated ERK, Akt and Src inhibitors to clarify the involvement of related each protein in migration and invasion ability, and we could observe that inhibitor treated cells showed suppressed migration and invasion ability. In vivo, TRPM7 knockdown cells projected decreased cell proliferation rate. Conclusions: Taken these results together, out study suggested TRPM7 might be an essential gene for prostate cancer metastasis by regulating prostate cancer cell proliferation, migration and invasion ability.

Keywords
Prostate cancer therapy
Transient receptor potential cation channel-subfamily M member 7
Migration ability
Cell proliferation
Src signaling
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