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Suppression of TRPM7 enhances TRAIL‐induced apoptosis in triple‐negative breast cancer cells
- Source :
- Journal of Cellular Physiology. 235:10037-10050
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Transient receptor potential cation channel subfamily M member 7 (TRPM7) composed of an ion channel and a kinase domain regulates triple-negative breast cancer (TNBC) cell migration, invasion, and metastasis, but it does not modulate TNBC proliferation. However, previous studies have shown that the combination treatment of nonselective TRPM7 channel inhibitors (2-aminoethoxydiphenyl borate and Gd3+ ) with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) increases antiproliferative effects and apoptosis in prostate cancer cells and hepatic stellate cells. We, therefore, investigated the potential role of TRPM7 in proliferation and apoptosis of TNBC cells (MDA-MB-231 and MDA-MB-468 cells) with TRAIL. We demonstrated that suppression of TRPM7 via TRPM7 knockdown or pharmacological inhibition synergistically increases TRAIL-induced antiproliferative effects and apoptosis in TNBC cells. Furthermore, we showed that the synergistic interaction might be associated with TRPM7 channel activities using combination treatments of TRAIL and TRPM7 inhibitors (NS8593 as a TRPM7 channel inhibitor and TG100-115 as a TRPM7 kinase inhibitor). We reveal that downregulation of cellular FLICE-inhibitory protein via inhibition of Ca2+ influx might be involved in the synergistic interaction. Our study would provide both a new role of TRPM7 in TNBC cell apoptosis and a potential combinatorial therapeutic strategy using TRPM7 inhibitors with TRAIL in the treatment of TNBC.
- Subjects :
- 0301 basic medicine
Physiology
Clinical Biochemistry
TRPM Cation Channels
Antineoplastic Agents
Apoptosis
Breast Neoplasms
Triple Negative Breast Neoplasms
Protein Serine-Threonine Kinases
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Cell Movement
TRPM7
Cell Line, Tumor
Hepatic Stellate Cells
Humans
Protein Kinase Inhibitors
Triple-negative breast cancer
Cell Proliferation
Chemistry
Kinase
Cell migration
Cell Biology
030104 developmental biology
030220 oncology & carcinogenesis
Hepatic stellate cell
Cancer research
Female
Tumor necrosis factor alpha
Subjects
Details
- ISSN :
- 10974652 and 00219541
- Volume :
- 235
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular Physiology
- Accession number :
- edsair.doi.dedup.....41922a9b476f3ac6c392e1bdfb0d5805