The regulatory and modulatory roles of TRP family channels in malignant tumors and relevant therapeutic strategies

Zhong, Tiecheng; Zhang, Wenxin; Guo, Hongjie; Pan, Xiaohui; Chen, Xi; He, Qiaojun; Yang, Bo; Ding, Ling

doi:10.1016/j.apsb.2021.11.001

Cited by 65 publications

(38 citation statements)

References 195 publications

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“…At the same time, the inhibition or enhancement of various TRP channels have been reported to exhibit good antitumor effects in vitro and in vivo [24,25]. Some targeted drugs have a close relationship with TRP family genes [26][27][28]. Thus, TRP channels are expected to be studied for developing pan−cancer-targeted therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, TRP channels are expected to be studied for developing pan−cancer-targeted therapy. With the in-depth understanding of the role of TRP channels in pan−cancer tissues, they have been reported to be the therapeutic targets in certain tumors [27] and are correlated with tumor progression and metastasis [26,29,30]. For example, TRPV4 is one of the members of the TRPV channel, which can detect mechanical pressure, osmotic pressure (hypotonic), medium temperature (>27 • C), and chemical stimulation and is a nonselective cation channel.…”

Section: Discussionmentioning

confidence: 99%

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Pan-Cancer Analysis of the TRP Family, Especially TRPV4 and TRPC4, and Its Expression Correlated with Prognosis, Tumor Microenvironment, and Treatment Sensitivity

et al. 2023

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Background: Transient receptor potential (TRP) channels are involved in various physiological, pathological, and tumorigenesis-related processes. However, only a few studies have comprehensively analyzed TRP family members and their association with prognosis and tumor microenvironment (TME) in various cancers. Thus, in this study, we focused on TRP channels in pan-cancer and screened two typical TRP channels, TRPV4 and TRPC4, as examples. Methods: Based on the latest public databases, we evaluated the expression level and prognostic value of TRP family genes in pan-cancer tissues via various bioinformatic analytical methods, and investigated the relationship between the expression of TRP family genes with TME, stemness score, immune subtype, drug sensitivity, and immunotherapy outcome in pan-cancer tissues. Results: Pan-cancer analysis revealed that the TRP family genes were differentially expressed in tumor and para-carcinoma tissues. A significant correlation existed between the expression of TRP family genes and prognosis. The expression of TRP family genes was significantly correlated with stromal, immune, RNA stemness, and DNA stemness scores in pan-cancer tissues. Our results indicated that the expression of TRP family genes correlated with the sensitivity to various drugs including PLX-4720, SB-590885, and HYPOTHEMYCIN, immunotherapy outcome, and immune-activation-related genes. Immunohistochemical analysis revealed significant differential expression of TRPV4 in bladder and para-carcinoma tissues. Conclusions: Our study elucidated the possible role of TRP family genes in cancer progression and provided insights for further studies on TRP family genes as potential pan-cancer targets to develop diagnostic and therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pan-Cancer Analysis of the TRP Family, Especially TRPV4 and TRPC4, and Its Expression Correlated with Prognosis, Tumor Microenvironment, and Treatment Sensitivity

et al. 2023

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“…They reduce the expression of TRPV6-initiated apoptosis and cell cycle arrest [ 33 ]. Impaired regulation of intracellular calcium resulting from the overexpression of TRPM8 can cause cell proliferation and metastasis but can also enhance drug-induced cell apoptosis [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

The Association between TRP Channels Expression and Clinicopathological Characteristics of Patients with Pancreatic Adenocarcinoma

Chelaru

Chiosa

Sorop

et al. 2022

IJMS

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Pancreatic adenocarcinoma (PDAC) has low survival rates worldwide due to its tendency to be detected late and its characteristic desmoplastic reaction, which slows the use of targeted therapies. As such, the discovery of new connections between genes and the clinicopathological parameters contribute to the search for new biomarkers or targets for therapy. Transient receptor potential (TRP) channels are promising tools for cancer therapy or markers for PDAC. Therefore, in this study, we selected several genes encoding TRP proteins previously reported in cellular models, namely, Transient Receptor Potential Cation Channel Subfamily V Member 6 (TRPV6), Transient receptor potential ankyrin 1 (TRPA1), and Transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8), as well as the TRPM8 Channel Associated Factor 1 (TCAF1) and TRPM8 Channel Associated Factor 2 (TCAF2) proteins, as regulatory factors. We analyzed the expression levels of tumors from patients enrolled in public datasets and confirmed the results with a validation cohort of PDAC patients enrolled in the Clinical Institute Fundeni, Romania. We found significantly higher expression levels of TRPA1, TRPM8, and TCAF1/F2 in tumoral tissues compared to normal tissues, but lower expression levels of TRPV6, suggesting that TRP channels have either tumor-suppressive or oncogenic roles. The expression levels were correlated with the tumoral stages and are related to the genes involved in calcium homeostasis (Calbindin 1 or S100A4) or to proteins participating in metastasis (PTPN1). We conclude that the selected TRP proteins provide new insights in the search for targets and biomarkers needed for therapeutic strategies for PDAC treatment.

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“…Several recent studies have investigated the effect of targeting TRP channels on PDAC growth. Research has found that the inhibition of TRPV4 reduced PDAC cell proliferation and migration and suppressed tumor growth [ 88 , 89 ]. According to a study, TRPM7 plays a partial role in the progressive and invasive nature of PDAC.…”

Section: Outcome and Implicationsmentioning

confidence: 99%

The Emergence of TRP Channels Interactome as a Potential Therapeutic Target in Pancreatic Ductal Adenocarcinoma

et al. 2023

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Integral membrane proteins, known as Transient Receptor Potential (TRP) channels, are cellular sensors for various physical and chemical stimuli in the nervous system, respiratory airways, colon, pancreas, bladder, skin, cardiovascular system, and eyes. TRP channels with nine subfamilies are classified by sequence similarity, resulting in this superfamily’s tremendous physiological functional diversity. Pancreatic Ductal Adenocarcinoma (PDAC) is the most common and aggressive form of pancreatic cancer. Moreover, the development of effective treatment methods for pancreatic cancer has been hindered by the lack of understanding of the pathogenesis, partly due to the difficulty in studying human tissue samples. However, scientific research on this topic has witnessed steady development in the past few years in understanding the molecular mechanisms that underlie TRP channel disturbance. This brief review summarizes current knowledge of the molecular role of TRP channels in the development and progression of pancreatic ductal carcinoma to identify potential therapeutic interventions.

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The regulatory and modulatory roles of TRP family channels in malignant tumors and relevant therapeutic strategies

Cited by 65 publications

References 195 publications

Pan-Cancer Analysis of the TRP Family, Especially TRPV4 and TRPC4, and Its Expression Correlated with Prognosis, Tumor Microenvironment, and Treatment Sensitivity

Pan-Cancer Analysis of the TRP Family, Especially TRPV4 and TRPC4, and Its Expression Correlated with Prognosis, Tumor Microenvironment, and Treatment Sensitivity

The Association between TRP Channels Expression and Clinicopathological Characteristics of Patients with Pancreatic Adenocarcinoma

The Emergence of TRP Channels Interactome as a Potential Therapeutic Target in Pancreatic Ductal Adenocarcinoma

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