Inhibition of Transient Receptor Potential Melastain 7 Enhances Apoptosis Induced by TRAIL in PC-3 cells

Lin, Chang-Ming; Ma, Jianjun; Zhang, Li; Hao, Zongyao; Zhou, Jun; Zhou, Zhenyu; Shi, Hao-Qiang; Zhang, Yifei; Shao, En-Ming; Liang, Chaozhao

doi:10.7314/apjcp.2015.16.10.4469

Cited by 20 publications

(21 citation statements)

References 31 publications

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“…We have previously shown that TRPM7 is associated with cell proliferation and survival of prostate cancer cells . Similarly, studies have also indicated that TRPM7 plays a key role in prostate cancer cells . Other studies have shown that TRPM7 is partially associated with epidermal growth factor (EGF)‐induced epithelial to mesenchymal transition (EMT) in breast cancer cells; however its role in EMT in prostate cancer is not well defined.…”

Section: Introductionmentioning

confidence: 99%

TGFβ‐induced epithelial‐to‐mesenchymal transition in prostate cancer cells is mediated via TRPM7 expression

Sun

Schaar

Sukumaran

et al. 2018

Molecular Carcinogenesis

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Growth factors, such as the transforming growth factor beta (TGFβ), play an important role in promoting metastasis of prostate cancer, thus understanding how TGFβ could induce prostate cancer cell migration may enable us to develop targeted strategies for treatment of advanced metastatic prostate cancer. To more clearly define the mechanism(s) involved in prostate cancer cell migration, we undertook a series of studies utilizing non‐malignant prostate epithelial cells RWPE1 and prostate cancer DU145 and PC3 cells. Our studies show that increased cell migration was observed in prostate cancer cells, which was mediated through epithelial‐to‐mesenchymal transition (EMT). Importantly, addition of Mg2+, but not Ca2+, increased cell migration. Furthermore, TRPM7 expression, which functions as an Mg2+ influx channel, was also increased in prostate cancer cells. Inhibition of TRPM7 currents by 2‐APB, significantly blocked cell migration in both DU145 and PC3 cells. Addition of growth factor TGFβ showed a further increase in cell migration, which was again blocked by the addition of 2‐APB. Importantly, TGFβ addition also significantly increased TRPM7 expression and function, and silencing of TRPM7 negated TGFβ‐induced cell migration along with a decrease in EMT markers showing loss of cell adhesion. Furthermore, resveratrol, which decreases prostate cancer cell migration, inhibited TRPM7 expression and function including TGFβ‐induced cell migration and activation of TRPM7 function. Together, these results suggest that Mg2+ influx via TRPM7 promotes cell migration by inducing EMT in prostate cancer cells and resveratrol negatively modulates TRPM7 function thereby inhibiting prostate cancer metastasis.

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Section: Introductionmentioning

confidence: 99%

TGFβ‐induced epithelial‐to‐mesenchymal transition in prostate cancer cells is mediated via TRPM7 expression

Sun

Schaar

Sukumaran

et al. 2018

Molecular Carcinogenesis

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“…When TRPM7 was activated by cholesterol, cell proliferation and migration of prostate cancer cells were increased [27]. In contrast, blockage of TRPM7 increased TNF-related apoptosis-inducing ligand-(TRAIL-) induced apoptosis of prostate cancer cells [28]. Our previous study also found a higher level of TRPM7 expression in androgen-independent prostate cancer cells comparing with normal prostate cells.…”

Section: Discussionmentioning

confidence: 81%

Suppression of TRPM7 Inhibited Hypoxia-Induced Migration and Invasion of Androgen-Independent Prostate Cancer Cells by Enhancing RACK1-Mediated Degradation of HIF-1α

Yang

Cai

Zhan

et al. 2020

Oxidative Medicine and Cellular Longevity

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Transient receptor potential melastatin subfamily member 7 (TRPM7) was essential in the growth and metastatic ability of prostate cancer cells. However, the effects and the relevant molecular mechanisms of TRPM7 on metastasis of prostate cancer under hypoxic atmosphere remain unclear. This study investigated the role of TRPM7 in the metastatic ability of androgen-independent prostate cancer cells under hypoxia. First, data mining was carried out to disclose the relationship between the TRPM7 gene level and the survival of prostate cancer patients. Specific siRNAs were used to knockdown target genes. Western blotting and qPCR were employed to determine protein and gene expression, respectively. The gene transcription activity was evaluated by luciferase activity assay of promoter gene. The protein interaction was determined by coimmunoprecipitation. Wound healing and transwell assays were employed to evaluated cell migration and invasion, respectively. Open access database results showed that high expression of TRPM7 was closely related to the poor survival of prostate cancer patients. Hypoxia simultaneously increased TRPM7 expression and induced HIF-1α accumulation in androgen-independent prostate cancer cells. Knockdown of TRPM7 significantly promoted HIF-1α degradation through the proteasome and inhibited EMT changes in androgen-independent prostate cancer cells under hypoxic condition. Moreover, TRPM7 knockdown increased the phosphorylation of RACK1 and strengthened the interaction between RACK1 and HIF-1α but attenuated the binding of HSP90 to HIF-1α. Whereas knockdown of RACK1 increased the binding of HSP90 to HIF-1α. Furthermore, both TRPM7 and HIF-1α knockdown significantly suppressed hypoxia-induced Annexin A1 protein expression, and suppression of HIF-1α/Annexin A1 signaling significantly inhibited hypoxia-induced cell migration and invasion of androgen-independent prostate cancer cells. Our findings demonstrate that TRPM7 knockdown promotes HIF-1α degradation via an oxygen-independent mechanism involving increased binding of RAKC1 to HIF-1α, and TRPM7-HIF-1α-Annexin A1 signaling axis plays a crucial role in the EMT, cell migration, and invasion of androgen-independent prostate cancer cells under hypoxic conditions.

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“…It has been reported that pharmacological inhibition (Gd 3+ and 2-APB) of TRPM7 increases TRAIL-induced antiproliferative effects in PC-3 and HSC-T6 cells and TRPM7 gene silencing increases TRAIL-induced antiproliferative effects in PC-3 cells (Lin et al, 2015;Liu et al, 2012). siTRPM7 significantly were increased about six-and five-fold higher, respectively, than those in cells transfected with scrambled siRNA at 1 ng/ml TRAIL.…”

Section: Silencing Of Trpm7 Increases Trail-induced Antiproliferatimentioning

confidence: 94%

Suppression of TRPM7 enhances TRAIL‐induced apoptosis in triple‐negative breast cancer cells

Song

Choi

et al. 2020

Journal Cellular Physiology

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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.

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Inhibition of Transient Receptor Potential Melastain 7 Enhances Apoptosis Induced by TRAIL in PC-3 cells

Cited by 20 publications

References 31 publications

TGFβ‐induced epithelial‐to‐mesenchymal transition in prostate cancer cells is mediated via TRPM7 expression

TGFβ‐induced epithelial‐to‐mesenchymal transition in prostate cancer cells is mediated via TRPM7 expression

Suppression of TRPM7 Inhibited Hypoxia-Induced Migration and Invasion of Androgen-Independent Prostate Cancer Cells by Enhancing RACK1-Mediated Degradation of HIF-1α

Suppression of TRPM7 enhances TRAIL‐induced apoptosis in triple‐negative breast cancer cells

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