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

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

doi:10.1016/j.canlet.2011.12.007

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

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

Research output: Contribution to journal › Article › peer-review

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Abstract

The transient receptor potential TRPM7 ion channel is required for cellular proliferation in pancreatic epithelia and adenocarcinoma. To elucidate the mechanism that mediates the function of TRPM7, we examined its role in survival of pancreatic cancer cells. RNA interference-mediated silencing of TRPM7 did not induce apoptotic cell death. TRPM7-deficient cells underwent replicative senescence with up-regulation of p16 ^CDKN2A and WRN mRNA. The combination of anti- TRPM7 siRNA and gemcitabine produced enhanced cytotoxicity as compared to gemcitabine alone. Thus, TRPM7 is required for preventing senescence, and modulation of TRPM7 expression may help improve treatment response of pancreatic cancer by combining with apoptosis-inducing agents.

Original language	English (US)
Pages (from-to)	99-105
Number of pages	7
Journal	Cancer Letters
Volume	318
Issue number	1
DOIs	https://doi.org/10.1016/j.canlet.2011.12.007
State	Published - May 1 2012

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.canlet.2011.12.007

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

abstract = "The transient receptor potential TRPM7 ion channel is required for cellular proliferation in pancreatic epithelia and adenocarcinoma. To elucidate the mechanism that mediates the function of TRPM7, we examined its role in survival of pancreatic cancer cells. RNA interference-mediated silencing of TRPM7 did not induce apoptotic cell death. TRPM7-deficient cells underwent replicative senescence with up-regulation of p16 CDKN2A and WRN mRNA. The combination of anti- TRPM7 siRNA and gemcitabine produced enhanced cytotoxicity as compared to gemcitabine alone. Thus, TRPM7 is required for preventing senescence, and modulation of TRPM7 expression may help improve treatment response of pancreatic cancer by combining with apoptosis-inducing agents.",

author = "Yee, {Nelson S.} and Weiqiang Zhou and Minsun Lee and Yee, {Rosemary K.}",

note = "Funding Information: N.S.Y. is supported by the Physician Scientist Stimulus Package from The Pennsylvania State University College of Medicine. This work was supported by the research start-up fund from the Penn State Hershey Cancer Institute (N.S.Y.), American Cancer Society (Grant IRG-77-004-31) administered through The Holden Comprehensive Cancer Center at The University of Iowa (N.S.Y.), and Cancer Center Support Grant (P30 CA 086862) by the National Cancer Institute to the Holden Comprehensive Cancer Center at the University of Iowa (N.S.Y.).",

year = "2012",

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doi = "10.1016/j.canlet.2011.12.007",

language = "English (US)",

volume = "318",

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T1 - Targeted silencing of TRPM7 ion channel induces replicative senescence and produces enhanced cytotoxicity with gemcitabine in pancreatic adenocarcinoma

AU - Yee, Nelson S.

AU - Zhou, Weiqiang

AU - Lee, Minsun

AU - Yee, Rosemary K.

N1 - Funding Information: N.S.Y. is supported by the Physician Scientist Stimulus Package from The Pennsylvania State University College of Medicine. This work was supported by the research start-up fund from the Penn State Hershey Cancer Institute (N.S.Y.), American Cancer Society (Grant IRG-77-004-31) administered through The Holden Comprehensive Cancer Center at The University of Iowa (N.S.Y.), and Cancer Center Support Grant (P30 CA 086862) by the National Cancer Institute to the Holden Comprehensive Cancer Center at the University of Iowa (N.S.Y.).

PY - 2012/5/1

Y1 - 2012/5/1

N2 - The transient receptor potential TRPM7 ion channel is required for cellular proliferation in pancreatic epithelia and adenocarcinoma. To elucidate the mechanism that mediates the function of TRPM7, we examined its role in survival of pancreatic cancer cells. RNA interference-mediated silencing of TRPM7 did not induce apoptotic cell death. TRPM7-deficient cells underwent replicative senescence with up-regulation of p16 CDKN2A and WRN mRNA. The combination of anti- TRPM7 siRNA and gemcitabine produced enhanced cytotoxicity as compared to gemcitabine alone. Thus, TRPM7 is required for preventing senescence, and modulation of TRPM7 expression may help improve treatment response of pancreatic cancer by combining with apoptosis-inducing agents.

AB - The transient receptor potential TRPM7 ion channel is required for cellular proliferation in pancreatic epithelia and adenocarcinoma. To elucidate the mechanism that mediates the function of TRPM7, we examined its role in survival of pancreatic cancer cells. RNA interference-mediated silencing of TRPM7 did not induce apoptotic cell death. TRPM7-deficient cells underwent replicative senescence with up-regulation of p16 CDKN2A and WRN mRNA. The combination of anti- TRPM7 siRNA and gemcitabine produced enhanced cytotoxicity as compared to gemcitabine alone. Thus, TRPM7 is required for preventing senescence, and modulation of TRPM7 expression may help improve treatment response of pancreatic cancer by combining with apoptosis-inducing agents.

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VL - 318

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JO - Cancer Letters

JF - Cancer Letters

IS - 1

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

Abstract

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