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The TRPC1 Channel Forms a PI3K/CaM Complex and Regulates Pancreatic Ductal Adenocarcinoma Cell Proliferation in a Ca(2+)-Independent Manner.

Abstract : Dysregulation of the transient receptor canonical ion channel (TRPC1) has been found in several cancer types, yet the underlying molecular mechanisms through which TRPC1 impacts pancreatic ductal adenocarcinoma (PDAC) cell proliferation are incompletely understood. Here, we found that TRPC1 is upregulated in human PDAC tissue compared to adjacent pancreatic tissue and this higher expression correlates with low overall survival. TRPC1 is, as well, upregulated in the aggressive PDAC cell line PANC-1, compared to a duct-like cell line, and its knockdown (KD) reduced cell proliferation along with PANC-1 3D spheroid growth by arresting cells in the G1/S phase whilst decreasing cyclin A, CDK2, CDK6, and increasing p21(CIP1) expression. In addition, the KD of TRPC1 neither affected Ca(2+) influx nor store-operated Ca(2+) entry (SOCE) and reduced cell proliferation independently of extracellular calcium. Interestingly, TRPC1 interacted with the PI3K-p85α subunit and calmodulin (CaM); both the CaM protein level and AKT phosphorylation were reduced upon TRPC1 KD. In conclusion, our results show that TRPC1 regulates PDAC cell proliferation and cell cycle progression by interacting with PI3K-p85α and CaM through a Ca(2+)-independent pathway.
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https://hal-u-picardie.archives-ouvertes.fr/hal-03740516
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Soumis le : vendredi 29 juillet 2022 - 15:17:24
Dernière modification le : vendredi 5 août 2022 - 11:25:09

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Alban Girault, Pierre Rybarczyk, Marie-Sophie Telliez, Stéphanie Guénin, Riad Tebbakha, et al.. The TRPC1 Channel Forms a PI3K/CaM Complex and Regulates Pancreatic Ductal Adenocarcinoma Cell Proliferation in a Ca(2+)-Independent Manner.. International Journal of Molecular Sciences, MDPI, 2022, 23 (14), pp.7923. ⟨10.3390/ijms23147923⟩. ⟨hal-03740516⟩

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