Targeting TRPV1 on cellular plasticity regulated by Ovol 2 and Zeb 1 in hepatocellular carcinoma

Xie, Chengzhi; Liu, Guoxing; Li, Min; Yu, Fang; Ke, Qing; Tang, Yu; Wu, Xiaolong; Lei, Xiaohua; Li, Xiaocheng; Liu, Qiang; Liu, Gao; Liu, Jiefeng; Zhang, Yueming; Huang, Zhao; Hu, Zecheng; Cao, Zhenyu; Hu, Jiarui; Huang, Shengfu; Zhong, Di; Huang, Jiaxin; Wu, Fang-Xiang; Wang, Jun; Mori, Masaki; Yamamoto, Hirofumi; Wang, Jianxin; Xu, Xundi

doi:10.1016/j.biopha.2019.109270

Cited by 17 publications

(14 citation statements)

References 32 publications

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“…TRPV1 might be controlling Zeb1 in pancreatic cancer as it has been shown in hepatocellular carcinoma. The knockout of TRPV1 channels in mice leads to an upregulation of Zeb1 and subsequent promotion of hepatocarcinogenesis [ 79 ]. So far, it is not known whether such a link between TRPV1 and Zeb1 also exists in PDAC.…”

Section: Trpv1mentioning

confidence: 99%

Role of the TRP Channels in Pancreatic Ductal Adenocarcinoma Development and Progression

Mesquita

Prevarskaya

Schwab³

et al. 2021

Cells

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The transient receptor potential channels (TRPs) have been related to several different physiologies that range from a role in sensory physiology (including thermo- and osmosensation) to a role in some pathologies like cancer. The great diversity of functions performed by these channels is represented by nine sub-families that constitute the TRP channel superfamily. From the mid-2000s, several reports have shown the potential role of the TRP channels in cancers of multiple origin. The pancreatic cancer is one of the deadliest cancers worldwide. Its prevalence is predicted to rise further. Disappointingly, the treatments currently used are ineffective. There is an urgency to find new ways to counter this disease and one of the answers may lie in the ion channels belonging to the superfamily of TRP channels. In this review, we analyse the existing knowledge on the role of TRP channels in the development and progression of pancreatic ductal adenocarcinoma (PDAC). The functions of these channels in other cancers are also considered. This might be of interest for an extrapolation to the pancreatic cancer in an attempt to identify potential therapeutic interventions.

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Section: Trpv1mentioning

confidence: 99%

Role of the TRP Channels in Pancreatic Ductal Adenocarcinoma Development and Progression

Mesquita

Prevarskaya

Schwab³

et al. 2021

Cells

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“…Together with other signaling pathways, changes in intracellular Ca 2+ can switch cell signaling from proliferation to apoptosis and cell death. Moreover, interventions causing a large influx of Ca 2+ across the plasma membrane, such as may arise from the pathologic or pharmacological activation of some TRP channels, also induces cell death [ 31 , 32 , 49 ].…”

Section: Role Of Intracellular Ca 2+ In Regulatmentioning

confidence: 99%

“…Pharmacological activation of TRPV1 provides a potential avenue for killing HCC cells, as suggested for some other cancers [ 31 , 32 , 100 ]. In many cell types, the activation of TRPV1 by capsaicin or other agonists enhances a large Ca 2+ entry which can induce apoptosis [ 31 , 32 , 100 ]. Capsaicin offers the advantage of being a natural product and like other potential agents, could be physically targeted to a liver tumor using drug-emitting bead transcatheter arterial chemoembolization (discussed above).…”

Section: Trpc6 Trpv4 and Trpv1 In The Progression Metastasis Anmentioning

confidence: 99%

“…In an early study, Miao and colleagues reported that the TRPV1R protein is expressed in human HCC tissue and provided some evidence that higher expression of TRPV1R is associated with better HCC prognosis [ 103 ]. More recently, the role of TRPV1 in HCC has been studied using TRPV1 KO mice, diethylnitrosamine and xenograft mouse models of HCC and HCC cell lines [ 32 ]. TRPV1 was identified in HepG2 and Huh-7 HCC cells and in human liver HCC tissue.…”

Section: Trpc6 Trpv4 and Trpv1 In The Progression Metastasis Anmentioning

confidence: 99%

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Targeting Ca2+ Signaling in the Initiation, Promotion and Progression of Hepatocellular Carcinoma

Ali

Rychkov

Barritt

2020

Cancers

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Hepatocellular carcinoma (HCC) is a considerable health burden worldwide and a major contributor to cancer-related deaths. HCC is often not noticed until at an advanced stage where treatment options are limited and current systemic drugs can usually only prolong survival for a short time. Understanding the biology and pathology of HCC is a challenge, due to the cellular and anatomic complexities of the liver. While not yet fully understood, liver cancer stem cells play a central role in the initiation and progression of HCC and in resistance to drugs. There are approximately twenty Ca2+-signaling proteins identified as potential targets for therapeutic treatment at different stages of HCC. These potential targets include inhibition of the self-renewal properties of liver cancer stem cells; HCC initiation and promotion by hepatitis B and C and non-alcoholic fatty liver disease (principally involving reduction of reactive oxygen species); and cell proliferation, tumor growth, migration and metastasis. A few of these Ca2+-signaling pathways have been identified as targets for natural products previously known to reduce HCC. Promising Ca2+-signaling targets include voltage-operated Ca2+ channel proteins (liver cancer stem cells), inositol trisphosphate receptors, store-operated Ca2+ entry, TRP channels, sarco/endoplasmic reticulum (Ca2++Mg2+) ATP-ase and Ca2+/calmodulin-dependent protein kinases. However, none of these Ca2+-signaling targets has been seriously studied any further than laboratory research experiments. The future application of more systematic studies, including genomics, gene expression (RNA-seq), and improved knowledge of the fundamental biology and pathology of HCC will likely reveal new Ca2+-signaling protein targets and consolidate priorities for those already identified.

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“…The transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel, has been shown to modulate the plasticity of hepatocyte. TRPV1 downregulation has been shown to be associated with activation of ZEB1 and inhibition of OVOL2 which promoted hepatocarcinogenesis in a SOX10-dependent manner [Xie et al, 2019]. Coordinated regulation of cell state by ZEB1-OVOL2-GRHL2 axis has been shown to be crucial for corneal endothelial cells and alteration in this axis results into posterior polymprphous corneal dystrophy (PPCD) characterized by aberrant activation of Wnt pathway, highlighting the role of ZEB1-OVOL2-GRHL2 axis in mediating cellular plasticity in corneal tissue homeostasis [Chung et al, 2019].…”

Section: Introductionmentioning

confidence: 99%

OVOL1/2: Drivers of Epithelial Differentiation in Development, Disease and Reprogramming

Saxena¹,

Srikrishnan²,

Celià-Terrassa³

et al. 2020

Preprint

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OVOL proteins (OVOL1 and OVOL2), vertebrate homologs of Drosophila OVO, are critical regulators of epithelial lineage determination and differentiation during embryonic development in tissues such as kidney, skin, mammary epithelia, testis. OVOL inhibits EMT and can promote MET; moreover, they can regulate the stemness of cancer cells, thus playing an important role during cancer cell metastasis. Due to their central role in differentiation and maintenance of epithelial lineage, OVOL overexpression has been shown to be capable of reprogramming fibroblasts to epithelial cells. Here, we review the roles of OVOL mediated epithelial differentiation across multiple contexts – embryonic development, cancer progression, and cellular reprogramming.

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Targeting TRPV1 on cellular plasticity regulated by Ovol 2 and Zeb 1 in hepatocellular carcinoma

Cited by 17 publications

References 32 publications

Role of the TRP Channels in Pancreatic Ductal Adenocarcinoma Development and Progression

Role of the TRP Channels in Pancreatic Ductal Adenocarcinoma Development and Progression

Targeting Ca2+ Signaling in the Initiation, Promotion and Progression of Hepatocellular Carcinoma

OVOL1/2: Drivers of Epithelial Differentiation in Development, Disease and Reprogramming

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