Cancers, Vol. 13, Pages 2395: Orai1 Channel Regulates Human-Activated Pancreatic Stellate Cell Proliferation and TGF β1 Secretion through the AKT Signaling Pathway
Cancers, Vol. 13, Pages 2395: Orai1 Channel Regulates Human-Activated Pancreatic Stellate Cell Proliferation and TGFβ1 Secretion through the AKT Signaling Pathway
Cancers doi: 10.3390/cancers13102395
Authors:
Silviya Radoslavova
Antoine Folcher
Thibaut Lefebvre
Kateryna Kondratska
Stéphanie Guénin
Isabelle Dhennin-Duthille
Mathieu Gautier
Natalia Prevarskaya
Halima Ouadid-Ahidouch
Activated pancreatic stellate cells (aPSCs), the crucial mediator of pancreatic desmoplasia, are characterized, among others, by high proliferative potential and abundant transforming growth factor β1 (TGFβ1) secretion. Over the past years, the involvement of Ca2+ channels in PSC pathophysiology has attracted great interest in pancreatic cancer research. We, thus, aimed to investigate the role of the Orai1 Ca2+ channel in these two PSC activation processes. Using the siRNA approach, we invalided Orai1 expression and assessed the channel functionality by Ca2+ imaging, the effect on aPSC proliferation, and TGFβ1 secretion. We demonstrated the functional expression of the Orai1 channel in human aPSCs and its implication in the store-operated Ca2+ entry (SOCE). Orai1 silencing led to a decrease in aPSC proliferation, TGFβ1 secretion, and AKT activation. Interestingly, TGFβ1 induced a higher SOCE response by increasing Orai1 mRNAs and proteins and promoted both AKT phosphorylation and cell proliferation, abolished by Orai1 silencing. Together, our results highlight the rol...
Source: Cancers - Category: Cancer & Oncology Authors: Silviya Radoslavova Antoine Folcher Thibaut Lefebvre Kateryna Kondratska St éphanie Guénin Isabelle Dhennin-Duthille Mathieu Gautier Natalia Prevarskaya Halima Ouadid-Ahidouch Tags: Article Source Type: research