Transient Receptor Potential Channels in the Epithelial-to-Mesenchymal Transition

Eynde, Charlotte Van den; Clercq, Katrien De; Vriens, Joris

doi:10.3390/ijms22158188

Cited by 18 publications

(7 citation statements)

References 103 publications

(116 reference statements)

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“…Hence, alterations in this TRP channel expression pattern could have vast effects on their behavior, possibly facilitating malignant behavior. An overview of the current knowledge of TRP channel expression and activity in cellular phenotype and EMT is provided elsewhere [ 14 ]. In line herewith, modifications in TRP channel expression have been observed in several cancer types like prostate cancer, breast cancer and colon cancer [ 6 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

TRP channel expression correlates with the epithelial–mesenchymal transition and high-risk endometrial carcinoma

Eynde

Clercq

Bree

et al. 2021

Cell. Mol. Life Sci.

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Transient receptor potential (TRP) channels excel in cellular sensing as they allow rapid ion influx across the plasma membrane in response to a variety of extracellular cues. Recently, a distinct TRP mRNA expression signature was observed in stromal cells (ESC) and epithelial cells (EEC) of the endometrium, a tissue in which cell phenotypic plasticity is essential for normal functioning. However, it is unknown whether TRP channel mRNA expression is subject to the phenotypic switching that occurs during epithelial to mesenchymal transition (EMT) and mesenchymal to epithelial transition (MET), and whether TRP channel mRNA expression is associated with aggressive phenotypes in endometrial cancer (EC). Here, we induced EMT and MET in vitro using in primary EEC and ESC, respectively, and analyzed expression and functionality of TRP channels using RT-qPCR and intracellular Ca2+ imaging. The outcome of these experiments showed a strong association between TRPV2 and TRPC1 mRNA expression and the mesenchymal phenotype, whereas TRPM4 mRNA expression correlated with the epithelial phenotype. In line herewith, increased TRPV2 and TRPC1 mRNA expression levels were observed in both primary and metastatic EC biopsies and in primary EC cells with a high EMT status, indicating an association with an aggressive tumor phenotype. Remarkably, TRPV2 mRNA expression in primary EC biopsies was associated with tumor invasiveness and cancer stage. In contrast, increased TRPM4 mRNA expression was observed in EC biopsies with a low EMT status and less aggressive tumor phenotypes. Taken together, this dataset proved for the first time that TRP channel mRNA expression is strongly linked to cellular phenotypes of the endometrium, and that phenotypic transitions caused by either experimental manipulation or malignancy could alter this expression in a predictable manner. These results implicate that TRP channels are viable biomarkers to identify high-risk EC, and potential targets for EC treatment.

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Section: Introductionmentioning

confidence: 99%

TRP channel expression correlates with the epithelial–mesenchymal transition and high-risk endometrial carcinoma

Eynde

Clercq

Bree

et al. 2021

Cell. Mol. Life Sci.

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“…The acquisition of an invasive phenotype through an EMT program is, in some cancer cells, regulated by Ca 2+ signaling (Pedri et al , 2021 ; Van den Eynde et al , 2021 ). In metastatic melanoma cells, we investigated whether the mechanistic basis for TRPV2‐mediated aggressive potential could rely on such reprogramming which, in this specific case, is referred as pseudo‐EMT since melanocytes are not epithelial cells and their invasive state may not be exclusively mesenchymal.…”

Section: Discussionmentioning

confidence: 99%

The mechanosensitive TRPV2 calcium channel promotes human melanoma invasiveness and metastatic potential

et al. 2023

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Melanoma is a highly aggressive cancer endowed with a unique capacity of rapidly metastasizing, which is fundamentally driven by aberrant cell motility behaviors. Discovering "migrastatics" targets, specifically controlling invasion and dissemination of melanoma cells during metastasis, is therefore of primary importance. Here, we uncover the prominent expression of the plasma membrane TRPV2 calcium channel as a distinctive feature of melanoma tumors, directly related to melanoma metastatic dissemination. In vitro as well as in vivo, TRPV2 activity is sufficient to confer both migratory and invasive potentials, while conversely TRPV2 silencing in highly metastatic melanoma cells prevents aggressive behavior. In invasive melanoma cells, TRPV2 channel localizes at the leading edge, in dynamic nascent adhesions, and regulates calcium-mediated activation of calpain and the ensuing cleavage of the adhesive protein talin, along with F-actin organization. In human melanoma tissues, TRPV2 overexpression correlates with advanced malignancy and poor prognosis, evoking a biomarker potential. Hence, by regulating adhesion and motility, the mechanosensitive TRPV2 channel controls melanoma cell invasiveness, highlighting a new therapeutic option for migrastatics in the treatment of metastatic melanoma.

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“…Ion channels play critical roles in the generation and facilitation of the transmission of information within various tissues and cells (21). There is evidence to suggest that the abnormal modulation of ion channels and ancillary proteins could lead to serious diseases, including multiple cancers (22,23). Pivotal roles have been indicated for a variety of ion channels, including KCNE, in the development of several tumors.…”

Section: Discussionmentioning

confidence: 99%

Potassium voltage‑gated channel subfamily E member 4 facilitates the malignant progression of colon cancer by enhancing EGF containing fibulin extracellular matrix protein 2 expression

Wang

Zhao

2023

Exp Ther Med

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Colon cancer is a highly invasive and metastatic cancer with a poor prognosis. The University of Alabama at Birmingham Cancer data analysis portal (UALCAN) database indicates that potassium voltage-gated channel subfamily E member 4 (KCNE4) is highly expressed in colon cancer tissues. UALCAN data also show that KCNE4 expression is positively associated with individual cancer stages and negatively associated with patient survival. Therefore, the aim of the current study was to elucidate the functional role of KCNE4 in the biological behaviors of colon cancer cells and to investigate the underlying molecular mechanism. The gene EGF containing fibulin extracellular matrix protein 2 (EFEMP2) was found to be positively correlated with KCNE4 in colon cancer based on analysis performed using the LinkedOmics database; notably, upregulated EFEMP2 expression has been reported to be closely associated with the malignant phenotypes of colon cancer cells. The differences in the expression levels of KCNE4 and EFEMP2 between human colon cancer and normal colonic mucosa cell lines were assessed via reverse transcription-quantitative PCR and western blot assays. In addition, the proliferation, migration and invasion of colon cancer cells were determined using Cell Counting kit-8, colony formation, would healing and Transwell assays, and a co-immunoprecipitation assay was performed to confirm the interaction between KCNE4 and EFEMP2. The results of the study demonstrated that KCNE4 and EFEMP2 are markedly upregulated in colon cancer cells. In addition, KCNE4 interacted with and bound to EFEMP2. The suppressive effects of KCNE4 knockdown on the proliferation, colony formation, migration and invasion of colon cancer cells were attenuated by EFEMP2 overexpression. On the basis of these findings, it may be concluded that KCNE4 acts as an oncogene in colon cancer via the promotion of EFEMP2 expression.

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Transient Receptor Potential Channels in the Epithelial-to-Mesenchymal Transition

Cited by 18 publications

References 103 publications

TRP channel expression correlates with the epithelial–mesenchymal transition and high-risk endometrial carcinoma

TRP channel expression correlates with the epithelial–mesenchymal transition and high-risk endometrial carcinoma

The mechanosensitive TRPV2 calcium channel promotes human melanoma invasiveness and metastatic potential

Potassium voltage‑gated channel subfamily E member 4 facilitates the malignant progression of colon cancer by enhancing EGF containing fibulin extracellular matrix protein 2 expression

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