Silencing of TRPM8 inhibits aggressive tumor phenotypes and enhances gemcitabine sensitivity in pancreatic cancer

Liu, JieFeng; Hu, Guo‐Huang; Gong, Yujing; Yu, Qianle; He, Bin; Li, WangHao; Zhou, He; Hao, WenJie; He, ZiChao; Liu, Yiping

doi:10.1016/j.pan.2018.08.011

Cited by 24 publications

(38 citation statements)

References 28 publications

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“…TRPM8 protein was found to be upregulated in human pancreatic adenocarcinoma cell lines and tissues [94,95]. Other studies further confirmed the upregulation of TRPM8 in pancreatic cancer tissues in human patients compared to adjacent tissues [96,97]. In addition, high TRPM8 protein expression was found to be associated with lower overall survival and poor disease free survival values for pancreatic cancer patients [97], as well as positively correlated with the tumor size and stage of pancreatic cancer [94].…”

Section: Pancreatic Cancermentioning

confidence: 69%

“…These findings suggest that the activation of TRPV1 could potentially enhance standard therapies. Furthermore, targeting other TRP channels showed an amplification of the effects of commonly used chemotherapeutics [77,96,101,115,126,154], potentially providing an option for the enhancement of current therapeutic strategies. Currently, several clinical trials evaluating ion channel inhibitors and blockers are ongoing [158,162,163].…”

Section: Discussionmentioning

confidence: 99%

“…It was also further shown that TRPM8 mediates Ca 2+ influx in PANC-1 and BxPC-3 cell lines and plays a role in proliferation as well as migration. Additionally, targeting TRPM8 in PANC-1 and BxPC-3 with siRNA resulted in an enhancement of gemcitabine cytotoxicity, which was accompanied by a change in the expression of apoptosis-and gemcitabine metabolism-related proteins [96]. Another study further showed that targeting TRPM8 with shRNA in BxPC-3 and MIA PaCa-2 resulted in a decrease in invasion [94].…”

Section: Pancreatic Cancermentioning

confidence: 93%

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TRP Channels in Digestive Tract Cancers

Stokłosa

Borgström

Kappel

et al. 2020

IJMS

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Cancers of the digestive tract are among the most prevalent types of cancer. These types of cancers are often diagnosed at a late stage, which results in a poor prognosis. Currently, many biomedical studies focus on the role of ion channels, in particular transient receptor potential (TRP) channels, in cancer pathophysiology. TRP channels show mostly non-selective permeability to monovalent and divalent cations. TRP channels are often dysregulated in digestive tract cancers, which can result in alterations of cancer hallmark functions, such as enhanced proliferation, migration, invasion and the inability to induce apoptosis. Therefore, TRP channels could serve as potential diagnostic biomarkers. Moreover, TRP channels are mostly expressed on the cell surface and ion channel targeting drugs do not need to enter the cell, making them attractive candidate drug targets. In this review, we summarize the current knowledge about TRP channels in connection to digestive tract cancers (oral cancer, esophageal cancer, liver cancer, pancreatic cancer, gastric cancer and colorectal cancer) and give an outlook on the potential of TRP channels as cancer biomarkers or therapeutic targets.

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Section: Pancreatic Cancermentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Pancreatic Cancermentioning

confidence: 93%

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TRP Channels in Digestive Tract Cancers

Stokłosa

Borgström

Kappel

et al. 2020

IJMS

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“…TRPM8 is necessary for proliferation and invasion of PCa cells and is closely related to PCa gemcitabine sensitivity [61]. In PCa cell lines, PACN-1 and BxPC-3 sensitivity to gemcitabine is increased, while proliferation and invasion have been suppressed after TRPM8 RNA interference-mediated silencing.…”

Section: Trpm Channels In Cancer Therapymentioning

confidence: 99%

Transient Receptor Potential Cation Channels in Cancer Therapy

et al. 2019

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In mammals, the transient receptor potential (TRP) channels family consists of six different families, namely TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPML (mucolipin), TRPP (polycystin), and TRPA (ankyrin), that are strictly connected with cancer cell proliferation, differentiation, cell death, angiogenesis, migration, and invasion. Changes in TRP channels’ expression and function have been found to regulate cell proliferation and resistance or sensitivity of cancer cells to apoptotic-induced cell death, resulting in cancer-promoting effects or resistance to chemotherapy treatments. This review summarizes the data reported so far on the effect of targeting TRP channels in different types of cancer by using multiple TRP-specific agonists, antagonists alone, or in combination with classic chemotherapeutic agents, microRNA specifically targeting the TRP channels, and so forth, and the in vitro and in vivo feasibility evaluated in experimental models and in cancer patients. Considerable efforts have been made to fight cancer cells, and therapies targeting TRP channels seem to be the most promising strategy. However, more in-depth investigations are required to completely understand the role of TRP channels in cancer in order to design new, more specific, and valuable pharmacological tools.

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“…1 Pancreatic cancer has a poor prognosis as PC progresses rapidly and metastasizes even in the early stages. 2 On the other hand, current systemic therapy for PC is limited and with a modest efficacy. 3 Moreover, patients with PC frequently obtain multidrug resistance.…”

Section: Introductionmentioning

confidence: 99%

MiR-203a-3p Inhibits Pancreatic Cancer Cell Proliferation, EMT, and Apoptosis by Regulating SLUG

Zheng

2020

Technol Cancer Res Treat

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Objective: The aim of the present research is to study the roles of miR-203a-3p on cell proliferation, migration, invasion, and epithelial–mesenchymal transition in pancreatic cancer. Methods: Transcription profiles were acquired from Gene Expression Omnibus database, which was used to screen out the differentially expressed microRNAs and messenger RNAs in pancreatic cancer. Pancreatic cancer tissues were used to verify the bioinformatics results by quantitative real-time polymerase chain reaction. The relationship between miR-203a-3p and SLUG was examined by TargetScan software, dual-luciferase reporter assay, and RNA immunoprecipitation. The Cell Counting Kit-8, wound healing, and transwell assays were conducted to investigate the proliferation, migration, and invasion capability of pancreatic cancer cells, respectively. The expression of epithelial–mesenchymal transition–related proteins was determined by the Western blot assay. Xenograft assay was performed to verify findings from in vitro assays. Results: Bioinformatic analysis found that a total of 113 microRNAs and 1749 messenger RNAs expressed differentially in pancreatic cancer tissues. Among these microRNAs, the expression of miR-203a-3p was significantly decreased in both pancreatic cancer tissues and cells. On the other hand, the SLUG expression was remarkably upregulated in pancreatic cancer tissues and cells in comparison with normal tissues and cells. Moreover, TargetScan software, dual-luciferase reporter assay, and RNA immunoprecipitation revealed that SLUG was a target of miR-203a-3p. The upregulation of miR-203a-3p expression inhibited the proliferation, migration, and invasion ability of pancreatic cancer cells by suppressing the epithelial–mesenchymal transition process via sponging SLUG. Conclusion: These findings indicate that downregulation of miR-203a-3p in pancreatic cancer cells leads to high expression of SLUG, which promotes epithelial–mesenchymal transition process and induces cancer progression.

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Silencing of TRPM8 inhibits aggressive tumor phenotypes and enhances gemcitabine sensitivity in pancreatic cancer

Cited by 24 publications

References 28 publications

TRP Channels in Digestive Tract Cancers

TRP Channels in Digestive Tract Cancers

Transient Receptor Potential Cation Channels in Cancer Therapy

MiR-203a-3p Inhibits Pancreatic Cancer Cell Proliferation, EMT, and Apoptosis by Regulating SLUG

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