Mutations in calmodulin-binding domains of TRPV4/6 channels confer invasive properties to colon adenocarcinoma cells

Arbabian, Atousa; Iftinca, Mircea; Altier, Christophe; Singh, Param Priya; Isambert, Hervé; Coscoy, Sylvie

doi:10.1080/19336950.2020.1740506

Cited by 16 publications

(17 citation statements)

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“…Moreover, the functions of TRPV4 are different or even opposite in different tumors. TRPV4 plays an oncogenic role in breast cancer, endometrial cancer, gastric cancer, oral squamous cell carcinoma, and COAD ( Arbabian et al, 2020 ; Azimi et al, 2020 ; Fujii et al, 2020 ; Li et al, 2020 ; Wang et al, 2020 ) and a suppressor gene role in glioma ( Huang et al, 2021 ). However—in many other tumor types—the function of TRPV4 remains unclear.…”

Section: Discussionmentioning

confidence: 99%

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TRPV4 is a Prognostic Biomarker that Correlates with the Immunosuppressive Microenvironment and Chemoresistance of Anti-Cancer Drugs

Wang

Feng

Zheng

et al. 2021

Front. Mol. Biosci.

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Background: Transient receptor potential cation channel subfamily V member 4 (TRPV4) has been reported to regulate tumor progression in many tumor types. However, its association with the tumor immune microenvironment remains unclear.Methods: TRPV4 expression was assessed using data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database. The clinical features and prognostic roles of TRPV4 were assessed using TCGA cohort. Gene set enrichment analysis (GSEA) of TRPV4 was conducted using the R package clusterProfiler. We analyzed the association between TRPV4 and immune cell infiltration scores of TCGA samples downloaded from published articles and the TIMER2 database. The IC50 values of 192 anti-cancer drugs were downloaded from the Genomics of Drug Sensitivity in Cancer (GDSC) database and the correlation analysis was performed.Results: TRPV4 was highly expressed and associated with worse overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI) in colon adenocarcinoma (COAD) and ovarian cancer. Furthermore, TRPV4 expression was closely associated with immune regulation-related pathways. Moreover, tumor-associated macrophage (TAM) infiltration levels were positively correlated with TRPV4 expression in TCGA pan-cancer samples. Immunosuppressive genes such as PD-L1, PD-1, CTLA4, LAG3, TIGIT, TGFB1, and TGFBR1 were positively correlated with TRPV4 expression in most tumors. In addition, patients with high expression of TRPV4 might be resistant to the treatment of Cisplatin and Oxaliplatin.Conclusion: Our results suggest that TRPV4 is an oncogene and a prognostic marker in COAD and ovarian cancer. High TRPV4 expression is associated with tumor immunosuppressive status and may contribute to TAM infiltration based on TCGA data from pan-cancer samples. Patients with high expression of TRPV4 might be resistant to the treatment of Cisplatin and Oxaliplatin.

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Section: Discussionmentioning

confidence: 99%

“…In COAD and ovarian cancer, TRPV4 was over-expressed; moreover, high expression levels of TRPV4 predicted worse OS in tumor patients. It has been reported that TRPV4 promotes the progression of COAD ( Arbabian et al, 2020 ), while no reports on TRPV4 in ovarian cancer are available.…”

Section: Discussionmentioning

confidence: 99%

TRPV4 is a Prognostic Biomarker that Correlates with the Immunosuppressive Microenvironment and Chemoresistance of Anti-Cancer Drugs

Wang

Feng

Zheng

et al. 2021

Front. Mol. Biosci.

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“…Moreover, the functions of TRPV4 are different or even opposite in different tumors. TRPV4 plays an oncogenic role in breast cancer, endometrial cancer, gastric cancer, oral squamous cell carcinoma, and COAD [2,[9][10][11][12] and a suppressor gene role in glioma [1]. However-in many other tumor types-the function of TRPV4 remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…In COAD and ovarian cancer, TRPV4 was overexpressed; moreover, high expression levels of TRPV4 predicted worse OS in tumor patients. It has been reported that TRPV4 promotes the progression of COAD [12], while no reports on TRPV4 in ovarian cancer are available.…”

Section: Discussionmentioning

confidence: 99%

TRPV4 is a Prognostic Biomarker That Correlates With the Immunosuppressive Microenvironment and Chemoresistance of Anti-Cancer Drugs

Wang

Feng²,

Zheng³

et al. 2021

Preprint

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Background: Transient receptor potential cation channel subfamily V member 4 (TRPV4) has been reported to regulate tumor progression in many tumor types. However, its association with the tumor immune microenvironment remains unclear.Methods: TRPV4 expression was assessed using data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database. The clinical features and prognostic roles of TRPV4 were assessed using TCGA cohort. Gene set enrichment analysis (GSEA) of TRPV4 was conducted using the R package clusterProfiler. We analyzed the association between TRPV4 and immune cell infiltration scores of TCGA samples downloaded from published articles and the TIMER2 database.Results: TRPV4 was highly expressed and associated with worse overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI) in colon adenocarcinoma (COAD) and ovarian cancer. Furthermore, TRPV4 expression was closely associated with immune regulation-related pathways. Moreover, tumor-associated macrophage (TAM) infiltration levels were positively correlated with TRPV4 expression in TCGA pan-cancer samples. Immunosuppressive genes such as PD-L1, PD-1, CTLA4, LAG3, TIGIT, TGFB1, and TGFBR1 were positively correlated with TRPV4 expression in most tumors.Conclusions: Our results suggest that TRPV4 is an oncogene and a prognostic marker in COAD and ovarian cancer. High TRPV4 expression is associated with tumor immunosuppressive status and may contribute to TAM infiltration based on TCGA data from pan-cancer samples.

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“…Ohnologs and Diseases Ohnologs preserved in the human genome are dosage-sensitive genes [137][138][139]. Sensitivity to gene dosage may provide a key to the pathogenesis of many disorders and therefore arouses increasing interest [138].…”

Section: Clinical Significance Of Whole-genome Duplicationsmentioning

confidence: 99%

Whole-Genome Duplications in Evolution, Ontogeny, and Pathology: Complexity and Emergency Reserves

Anatskaya

Vinogradov

2021

Mol Biol

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Whole-genome duplication (WGD), or polyploidy, increases the amount of genetic information in the cell. WGDs of whole organisms are found in all branches of eukaryotes and act as a driving force of speciation, complication, and adaptations. Somatic-cell WGDs are observed in all types of tissues and can result from normal or altered ontogenetic programs, regeneration, pathological conditions, aging, malignancy, and metastasis. Despite the versatility of WGDs, their functional significance, general properties, and causes of their higher adaptive potential are unclear. Comparisons of whole-transcriptome data and information from various fields of molecular biology, genomics, and molecular medicine showed several common features for polyploidy of organisms and somatic and cancer cells, making it possible to understand what WGD properties lead to the emergence of an adaptive phenotype. The adaptation potential of WGDs may be associated with an increase in the complexity of the regulation of networks and signaling systems; a higher resistance to stress; and activation of ancient evolutionary programs of unicellularity and pathways of morphogenesis, survival, and life extension. A balance between the cell and organismal levels in controlling gene regulation may shift in stress towards the priority of cell survival, and the shift can lead to cardiovascular diseases and carcinogenesis. The presented information helps to understand how polyploidy creates new phenotypes and why it acts as a driving force of evolution and an important regulator of biological processes in somatic cells during ontogeny, pathogenesis, regeneration, and transformation.

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Mutations in calmodulin-binding domains of TRPV4/6 channels confer invasive properties to colon adenocarcinoma cells

Abstract: Coscoy (2020) Mutations in calmodulin-binding domains of TRPV4/6 channels confer invasive properties to colon adenocarcinoma cells, Channels, 14:1, 101-109,

Cited by 16 publications

References 44 publications

TRPV4 is a Prognostic Biomarker that Correlates with the Immunosuppressive Microenvironment and Chemoresistance of Anti-Cancer Drugs

TRPV4 is a Prognostic Biomarker that Correlates with the Immunosuppressive Microenvironment and Chemoresistance of Anti-Cancer Drugs

TRPV4 is a Prognostic Biomarker That Correlates With the Immunosuppressive Microenvironment and Chemoresistance of Anti-Cancer Drugs

Whole-Genome Duplications in Evolution, Ontogeny, and Pathology: Complexity and Emergency Reserves

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