ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2024; 15(10):2891-2899. doi:10.7150/jca.93940 This issue Cite
Research Paper
TRPV3 regulates Breast Cancer Cell Proliferation and Apoptosis by EGFR/AKT pathway
1. Basic Medicine College of Daqing Campus, Harbin Medical University-Daqing, Daqing, 163319, China.
2. Department of Pharmacology, Hainan Medical University, Haikou, 571199, China.
3. Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, 02215, United States of America.
4. Department of Pharmacy, The First Affiliated Hospital, Jinan University, Guangzhou, 510630, China.
5. The Guangzhou Key Laboratory of Basic and Translational Research on Chronic Diseases, Jinan University, Guangzhou, 510630, China.
*Yan Xie, Hyo In Kim and Qianzhi Yang have contributed equally to this work.
Abstract
Breast cancer (BC) is one of the most common cancer types worldwide and the first cause of cancer-related deaths in women. Transient receptor potential vanillin 3 (TRPV3) has been preliminarily discovered to play an important role in various cancers, including BC. Here, we explored the effect of TRPV3 on breast cancer cells and its potential mechanism. TRPV3 level was measured in BC tissue and adjacent noncancerous breast tissue using real-time RT-PCR and Western blot. Wound healing was used to detect cell migration. MTT and EDU were detected cell proliferation. TUNEL and Caspase-3 activity were used to detect cell apoptosis. We found that TRPV3 expression significantly increased in both human BC tissues and breast cells line. TRPV3 siRNA (TRPV3 inhibition) dramatically suppressed cell migration and proliferation, promoted the apoptosis, and decreased [Ca2+]i; whereas Carvacrol (TRPV3 agonist) has opposite effect in MCF-7 cells. We validated EGFR (Epidermal growth factor receptor) is a direct target protein of TRPV3. Mechanism studies have shown that Carvacrol increased phosphorylation levels of EGFR and AKT, and were decreased by suppression of TRPV3. Moreover, Erlotinib (EGFR inhibitor) and LY294002 (PI3K inhibitor) diminished Carvacrol induced cell migration and proliferation, promoted cell apoptosis, and increased [Ca2+]i in Carvacrol group. Our results collectively suggest that TRPV3 siRNA inhibits migration and proliferation, and promoted apoptosis in breast cancer cells by EGFR/AKT pathway. These findings indicate that TRPV3 may represent a novel therapeutic strategy for breast cancer.
Keywords: breast cancer, TRPV3, EGFR, apoptosis, proliferation
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