Targeted silencing of TRPM7 ion channel induces replicative senescence and produces enhanced cytotoxicity with gemcitabine in pancreatic adenocarcinoma

Yee, Nelson S.; Zhou, Weiqiang; Lee, Minsun; Yee, Rosemary K.

doi:10.1016/j.canlet.2011.12.007

Cited by 57 publications

(54 citation statements)

References 42 publications

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“…Therefore, TRPC6 could potentially be of importance in the progression of IVD degeneration linked to cell senescence, but further studies are needed. In fact, the role of TRP channels in modulating senescence is also known for other cell types, such as endothelial cells (TRPC5) [47], pancreatic adenocarcinoma cells (TRPM7, TRPM8) [48,49] and lung fibroblasts (TRPC6) [30].…”

Section: Discussionmentioning

confidence: 99%

TRPC6 in simulated microgravity of intervertebral disc cells

et al. 2018

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Purpose Prolonged bed rest and microgravity in space cause intervertebral disc (IVD) degeneration. However, the underlying molecular mechanisms are not completely understood. Transient receptor potential canonical (TRPC) channels are implicated in mechanosensing of several tissues, but are poorly explored in IVDs. Methods Primary human IVD cells from surgical biopsies composed of both annulus fibrosus and nucleus pulposus (passage 1-2) were exposed to simulated microgravity and to the TRPC channel inhibitor SKF-96365 (SKF) for up to 5 days. Proliferative capacity, cell cycle distribution, senescence and TRPC channel expression were analyzed. Results Both simulated microgravity and TRPC channel antagonism reduced the proliferative capacity of IVD cells and induced senescence. While significant changes in cell cycle distributions (reduction in G1 and accumulation in G2/M) were observed upon SKF treatment, the effect was small upon 3 days of simulated microgravity. Finally, downregulation of TRPC6 was shown under simulated microgravity. Conclusions Simulated microgravity and TRPC channel inhibition both led to reduced proliferation and increased senescence. Furthermore, simulated microgravity reduced TRPC6 expression. IVD cell senescence and mechanotransduction may hence potentially be regulated by TRPC6 expression. This study thus reveals promising targets for future studies.Graphical abstract These slides can be retrieved under Electronic Supplementary Material.

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Section: Discussionmentioning

confidence: 99%

TRPC6 in simulated microgravity of intervertebral disc cells

et al. 2018

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“…For example, TRPM7 was found overexpressed in grade III breast cancer samples and promote breast cancer proliferation and migration (Dhennin-Duthille et al, 2011;Middelbeek et al, 2012). In pancreatic adenocarcinoma, TRPM7 was found highly up-regulated in cancer tissues and knockdown TRPM7 by small interference RNA induced cellular senescence (Rybarczyk et al, 2012;Yee et al, 2012b). In lung cancer, TRPM7 expression was up-regulated by epidermal growth factor (EGF) and plays a pivotal role in the migration of A549 cells (Gao et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of TRPM7 is Associated with Poor Prognosis in Human Ovarian Carcinoma

Wang¹,

Xiao²,

Luo³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: The melastatin-related transient receptor potential 7 channel (TRPM7) is a nonselective cation channel that has been shown to promote tumor metastasis and progression. In this study, we determined the expression of TRPM7 in ovarian carcinomas and investigated its possible prognostic value. Materials and Methods: Samples were collected from 138 patients with ovarian cancer. Expression of TRPM7 was assessed by real-time PCR and immunohistochemistry, expressed with reference to an established scoring system and related to clinical pathological factors. Kaplan-Meier survival analysis was applied to estimate disease-free survival (DFS) and overall survival (OS). Univariate and multivariate cox regression analyses were performed to correlate TRPM7 expression levels with DFS and OS. Results: TRPM7 was highly expressed in ovarian carcinoma and significantly associated with decreased disease-free survival (DFS: median 20 months vs. 42 months, P=0.0002) and overall survival (OS: median 27 months vs. 46 months, P<0.001). Conclusion: Overexpression of TRPM7 expression is significantly associated with poor prognosis in patients with ovarian cancer.

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“…In BxPC3 cells, silencing of TRPM7 by siRNA interference inhibited Mg 2+ fluorescence and blocked the migration, but (disappointingly) not the proliferation, of cancer cells (Rybarczyk et al, 2012). On a more positive note, in a second independent study, the combination of anti-TRPM7 siRNA and gemcitabine produced enhanced tumor cell killing compared with gemcitabine alone (Yee et al, 2012b). A subset of patients with pancreatic carcinoma aberrantly expresses TRPM8 (Yee et al, 2012a).…”

Section: G Transient Receptor Potential Channels In Cancermentioning

confidence: 98%