TRPV6 modulates proliferation of human pancreatic neuroendocrine BON-1 tumour cells

Skrzypski, Marek; Kołodziejski, Paweł; Mergler, Stefan; Khajavi, Noushafarin; Nowak, Krzysztof W.; Strowski, Mathias Z.

doi:10.1042/bsr20160106

Cited by 11 publications

(12 citation statements)

References 37 publications

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“…The presence of TRPV6 in neuroendocrine cancer cells mediates cell proliferation: TRPV6 downregulation reduces cell growth by approximately 30 % and leads to declined CCND1 and CDK4 expression, without affecting CCND2. TRPV6mediated cell proliferation is dependent upon NFAT-Ca 2+ activation as shown by TRPV6 downregulation [47]. These data are in accordance with previously reported role for TRPV6 in both prostate and breast cancer proliferation and growth.…”

Section: Trp Channels Netsupporting

confidence: 92%

“…Several TRP channels result de-regulated in cancer cells and have been suggested as valuable markers in predicting cancer progression and as potential targets for pharmaceutical therapy [7,44] . Concerning NET, TRP channels have been involved in neurosecretion and cell proliferation and in particular TRPM8, TRPV1 and TRPV6 in pancreatic NET BON cells lines as well as in primary PNET cells [45][46][47].…”

Section: Trp Channels Netmentioning

confidence: 99%

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Ca2+ Channel Toolkit in Neuroendocrine Tumors

Fiorio

Gkika

2019

Neuroendocrinology

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Neuroendocrine tumors (NET) constitute a heterogeneous group of malignancies with various clinical presentations and growth rates but a common origin in neuroendocrine cells located all over the body. NET are a relatively low-frequency disease mostly represented by gastroenteropancreatic (GEP) and bronchopulmonary tumors (pNET); on the other hand, an increasing frequency and prevalence have been associated with NET. Despite great efforts in recent years, the management of NET is still a critical unmet need due to the lack of knowledge of the biology of the disease, the lack of adequate biomarkers, late presentation, the relative insensitivity of imaging modalities, and a paucity of predictably effective treatment options. In this context Ca2+ signals, being pivotal molecular devices in sensing and integrating signals from the microenvironment, are emerging to be particularly relevant in cancer, where they mediate interactions between tumor cells and the tumor microenvironment to drive different aspects of neoplastic progression (e.g., cell proliferation and survival, cell invasiveness, and proangiogenetic programs). Indeed, ion channels represent good potential pharmacological targets due to their location on the plasma membrane, where they can be easily accessed by drugs. The present review aims to provide a critical and up-to-date overview of NET development integrating Ca2+ signal involvement. In this perspective, we first give an introduction to NET and Ca2+ channels and then describe the different families of Ca2+ channels implicated in NET, i.e., ionotropic receptors, voltage-dependent Ca2+ channels, and transient receptor potential channels, as well as intracellular Ca2+ channels and their signaling molecules.

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Section: Trp Channels Netsupporting

confidence: 92%

Section: Trp Channels Netmentioning

confidence: 99%

Ca2+ Channel Toolkit in Neuroendocrine Tumors

Fiorio

Gkika

2019

Neuroendocrinology

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“…Since these pathways were involved in β-cell proliferation (62,63), these data strongly suggested that TRPV6 may trigger INS-E cell growth via calcineurin/NFAT-and ERK1/2-dependent mechanisms. Notably, similar data indicating the link between TRPV6/NFAT signalling and cell proliferation were described in human neuroendocrine pancreatic BON cells (64). By contrast, to promitogenic effects of TRPV2 and TRPV6 in insulin producing cells, it was demonstrated that TRPV4 activation by hIAPP stimulate β-cell death.…”

Section: Trpvs In Controlling β-Cell Growth and Deathsupporting

confidence: 50%

Role of TRPV channels in regulating various pancreatic β-cell functions: Lessons from in vitro studies

Skrzypski

Billert

Mergler

et al. 2017

BST

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“…Knockdown or overexpression of TRPV6 in cultured cancer cells showed mixed effects in increasing/decreasing proliferation and/or apoptosis (Chow, Norng, Zhang, & Chai, 2007;V Lehen'Kyi, Flourakis, Skryma, & Prevarskaya, 2007;V. Lehen'kyi et al, 2012;Raphael et al, 2014;Skrzypski et al, 2016). Future studies are needed to clarify the role of TRPV6-[Ca 2+ ]i-PP2A in prostate and colon cancer initiation and progression and its relationship to IGF1 receptor-PI3 kinase-AKT-mTOR signaling.…”

Section: Discussionmentioning

confidence: 99%

Cell-autonomous regulation of epithelial cell quiescence by calcium channel Trpv6

Malick

et al. 2019

Preprint

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Epithelial homeostasis and regeneration require a pool of quiescent cells. How the quiescent cells are established and maintained is poorly understood. Here we report that Trpv6, a cation channel responsible for epithelial Ca 2+ absorption, functions as a key regulator of cellular quiescence. Genetic deletion and pharmacological blockade of Trpv6 promoted zebrafish epithelial cells to exit from quiescence and re-enter the cell cycle. Reintroducing Trpv6, but not its channel dead mutant, restored the quiescent state. Ca 2+ imaging showed that Trpv6 is constitutively open in vivo. Mechanistically, Trpv6-mediated Ca 2+ influx maintained the quiescent state by suppressing insulin-like growth factor (IGF)-mediated Akt and Tor signaling.In zebrafish epithelia and human colon cancer cells, Trpv6/TRPV6 elevated intracellular Ca 2+ levels and activated PP2A, which down-regulated IGF signaling and promoted the quiescent state. Our findings suggest that Trpv6 mediates constitutive Ca 2+ influx into epithelial cells to continuously suppress growth factor signaling and maintain the quiescent state.

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TRPV6 modulates proliferation of human pancreatic neuroendocrine BON-1 tumour cells

Cited by 11 publications

References 37 publications

Ca<sup>2+</sup> Channel Toolkit in Neuroendocrine Tumors

Ca<sup>2+</sup> Channel Toolkit in Neuroendocrine Tumors

Role of TRPV channels in regulating various pancreatic β-cell functions: Lessons from <i>in vitro</i> studies

Cell-autonomous regulation of epithelial cell quiescence by calcium channel Trpv6

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