PMID- 35887266
OWN - NLM
STAT- MEDLINE
DCOM- 20220728
LR  - 20240102
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 14
DP  - 2022 Jul 18
TI  - The TRPC1 Channel Forms a PI3K/CaM Complex and Regulates Pancreatic Ductal 
      Adenocarcinoma Cell Proliferation in a Ca(2+)-Independent Manner.
LID - 10.3390/ijms23147923 [doi]
LID - 7923
AB  - 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-p85alpha 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-p85alpha and CaM through a Ca(2+)-independent 
      pathway.
FAU - Schnipper, Julie
AU  - Schnipper J
AUID- ORCID: 0000-0002-4315-6043
AD  - Laboratory of Cellular and Molecular Physiology, UR UPJV 4667, University of 
      Picardie Jules Verne, 80000 Amiens, France.
FAU - Kouba, Sana
AU  - Kouba S
AD  - Laboratory of Cellular and Molecular Physiology, UR UPJV 4667, University of 
      Picardie Jules Verne, 80000 Amiens, France.
FAU - Hague, Frederic
AU  - Hague F
AD  - Laboratory of Cellular and Molecular Physiology, UR UPJV 4667, University of 
      Picardie Jules Verne, 80000 Amiens, France.
FAU - Girault, Alban
AU  - Girault A
AUID- ORCID: 0000-0001-5478-9340
AD  - Laboratory of Cellular and Molecular Physiology, UR UPJV 4667, University of 
      Picardie Jules Verne, 80000 Amiens, France.
FAU - Rybarczyk, Pierre
AU  - Rybarczyk P
AD  - Laboratory of Cellular and Molecular Physiology, UR UPJV 4667, University of 
      Picardie Jules Verne, 80000 Amiens, France.
AD  - Anatomy and Pathology Department, Amiens Hospital, University of Picardie Jules 
      Verne, Tumorotheque of Picardie, 80000 Amiens, France.
FAU - Telliez, Marie-Sophie
AU  - Telliez MS
AD  - Laboratory of Cellular and Molecular Physiology, UR UPJV 4667, University of 
      Picardie Jules Verne, 80000 Amiens, France.
FAU - Guenin, Stephanie
AU  - Guenin S
AUID- ORCID: 0000-0002-0514-982X
AD  - Centre de Ressources Regional en Biologie Moleculaire, Universite de Picardie 
      Jules Verne, 80000 Amiens, France.
FAU - Tebbakha, Riad
AU  - Tebbakha R
AD  - Laboratory of Cellular and Molecular Physiology, UR UPJV 4667, University of 
      Picardie Jules Verne, 80000 Amiens, France.
AD  - Anatomy and Pathology Department, Amiens Hospital, University of Picardie Jules 
      Verne, Tumorotheque of Picardie, 80000 Amiens, France.
FAU - Sevestre, Henri
AU  - Sevestre H
AD  - Laboratory of Cellular and Molecular Physiology, UR UPJV 4667, University of 
      Picardie Jules Verne, 80000 Amiens, France.
AD  - Anatomy and Pathology Department, Amiens Hospital, University of Picardie Jules 
      Verne, Tumorotheque of Picardie, 80000 Amiens, France.
FAU - Ahidouch, Ahmed
AU  - Ahidouch A
AD  - Laboratory of Cellular and Molecular Physiology, UR UPJV 4667, University of 
      Picardie Jules Verne, 80000 Amiens, France.
AD  - Biology Department, University Ibn Zohr, Agadir 80000, Morocco.
FAU - Pedersen, Stine Falsig
AU  - Pedersen SF
AUID- ORCID: 0000-0002-3044-7714
AD  - Section for Cell Biology and Physiology, Department of Biology, University of 
      Copenhagen, 1165 Copenhagen O, Denmark.
FAU - Ouadid-Ahidouch, Halima
AU  - Ouadid-Ahidouch H
AD  - Laboratory of Cellular and Molecular Physiology, UR UPJV 4667, University of 
      Picardie Jules Verne, 80000 Amiens, France.
LA  - eng
PT  - Journal Article
DEP - 20220718
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Calmodulin)
RN  - 0 (TRPC Cation Channels)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcium/metabolism
MH  - Calmodulin/metabolism
MH  - *Carcinoma, Pancreatic Ductal/genetics
MH  - Cell Proliferation
MH  - Humans
MH  - *Pancreatic Neoplasms/genetics
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - TRPC Cation Channels/genetics/metabolism
PMC - PMC9323718
OTO - NOTNLM
OT  - PI3K
OT  - TRPC1
OT  - calmodulin
OT  - cell cycle progression
OT  - cell proliferation
OT  - pancreatic ductal adenocarcinoma
OT  - spheroid growth
COIS- The authors declare no conflict of interest.
EDAT- 2022/07/28 06:00
MHDA- 2022/07/29 06:00
PMCR- 2022/07/18
CRDT- 2022/07/27 01:24
PHST- 2022/06/28 00:00 [received]
PHST- 2022/07/15 00:00 [revised]
PHST- 2022/07/17 00:00 [accepted]
PHST- 2022/07/27 01:24 [entrez]
PHST- 2022/07/28 06:00 [pubmed]
PHST- 2022/07/29 06:00 [medline]
PHST- 2022/07/18 00:00 [pmc-release]
AID - ijms23147923 [pii]
AID - ijms-23-07923 [pii]
AID - 10.3390/ijms23147923 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Jul 18;23(14):7923. doi: 10.3390/ijms23147923.