The TRPC1 Channel Forms a PI3K/CaM Complex and Regulates Pancreatic Ductal Adenocarcinoma Cell Proliferation in a Ca2+-Independent Manner

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

The TRPC1 Channel Forms a PI3K/CaM Complex and Regulates Pancreatic Ductal Adenocarcinoma Cell Proliferation in a Ca2+-Independent Manner. / Schnipper, Julie; Kouba, Sana; Hague, Frederic; Girault, Alban; Rybarczyk, Pierre; Telliez, Marie-Sophie; Guenin, Stephanie; Tebbakha, Riad; Sevestre, Henri; Ahidouch, Ahmed; Pedersen, Stine Falsig; Ouadid-Ahidouch, Halima.

In: International Journal of Molecular Sciences , Vol. 23, No. 14, 7923, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Schnipper, J, Kouba, S, Hague, F, Girault, A, Rybarczyk, P, Telliez, M-S, Guenin, S, Tebbakha, R, Sevestre, H, Ahidouch, A, Pedersen, SF & Ouadid-Ahidouch, H 2022, 'The TRPC1 Channel Forms a PI3K/CaM Complex and Regulates Pancreatic Ductal Adenocarcinoma Cell Proliferation in a Ca2+-Independent Manner', International Journal of Molecular Sciences , vol. 23, no. 14, 7923. https://doi.org/10.3390/ijms23147923

APA

Schnipper, J., Kouba, S., Hague, F., Girault, A., Rybarczyk, P., Telliez, M-S., Guenin, S., Tebbakha, R., Sevestre, H., Ahidouch, A., Pedersen, S. F., & Ouadid-Ahidouch, H. (2022). The TRPC1 Channel Forms a PI3K/CaM Complex and Regulates Pancreatic Ductal Adenocarcinoma Cell Proliferation in a Ca2+-Independent Manner. International Journal of Molecular Sciences , 23(14), [7923]. https://doi.org/10.3390/ijms23147923

Vancouver

Schnipper J, Kouba S, Hague F, Girault A, Rybarczyk P, Telliez M-S et al. The TRPC1 Channel Forms a PI3K/CaM Complex and Regulates Pancreatic Ductal Adenocarcinoma Cell Proliferation in a Ca2+-Independent Manner. International Journal of Molecular Sciences . 2022;23(14). 7923. https://doi.org/10.3390/ijms23147923

Author

Schnipper, Julie ; Kouba, Sana ; Hague, Frederic ; Girault, Alban ; Rybarczyk, Pierre ; Telliez, Marie-Sophie ; Guenin, Stephanie ; Tebbakha, Riad ; Sevestre, Henri ; Ahidouch, Ahmed ; Pedersen, Stine Falsig ; Ouadid-Ahidouch, Halima. / The TRPC1 Channel Forms a PI3K/CaM Complex and Regulates Pancreatic Ductal Adenocarcinoma Cell Proliferation in a Ca2+-Independent Manner. In: International Journal of Molecular Sciences . 2022 ; Vol. 23, No. 14.

Bibtex

@article{9c14d7adb1e846348347f0a8c728bcf3,
title = "The TRPC1 Channel Forms a PI3K/CaM Complex and Regulates Pancreatic Ductal Adenocarcinoma Cell Proliferation in a Ca2+-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 Ca2+ influx nor store-operated Ca2+ entry (SOCE) and reduced cell proliferation independently of extracellular calcium. Interestingly, TRPC1 interacted with the PI3K-p85 alpha 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-p85 alpha and CaM through a Ca2+-independent pathway.",
keywords = "pancreatic ductal adenocarcinoma, TRPC1, cell proliferation, spheroid growth, cell cycle progression, PI3K, calmodulin, CANONICAL 1 TRPC1, CALCIUM-CHANNELS, CANCER, EXPRESSION, CARCINOMA, CALMODULIN, MIGRATION, GROWTH, ENTRY",
author = "Julie Schnipper and Sana Kouba and Frederic Hague and Alban Girault and Pierre Rybarczyk and Marie-Sophie Telliez and Stephanie Guenin and Riad Tebbakha and Henri Sevestre and Ahmed Ahidouch and Pedersen, {Stine Falsig} and Halima Ouadid-Ahidouch",
year = "2022",
doi = "10.3390/ijms23147923",
language = "English",
volume = "23",
journal = "International Journal of Molecular Sciences (Online)",
issn = "1661-6596",
publisher = "MDPI AG",
number = "14",

}

RIS

TY - JOUR

T1 - The TRPC1 Channel Forms a PI3K/CaM Complex and Regulates Pancreatic Ductal Adenocarcinoma Cell Proliferation in a Ca2+-Independent Manner

AU - Schnipper, Julie

AU - Kouba, Sana

AU - Hague, Frederic

AU - Girault, Alban

AU - Rybarczyk, Pierre

AU - Telliez, Marie-Sophie

AU - Guenin, Stephanie

AU - Tebbakha, Riad

AU - Sevestre, Henri

AU - Ahidouch, Ahmed

AU - Pedersen, Stine Falsig

AU - Ouadid-Ahidouch, Halima

PY - 2022

Y1 - 2022

N2 - 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 Ca2+ influx nor store-operated Ca2+ entry (SOCE) and reduced cell proliferation independently of extracellular calcium. Interestingly, TRPC1 interacted with the PI3K-p85 alpha 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-p85 alpha and CaM through a Ca2+-independent pathway.

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 Ca2+ influx nor store-operated Ca2+ entry (SOCE) and reduced cell proliferation independently of extracellular calcium. Interestingly, TRPC1 interacted with the PI3K-p85 alpha 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-p85 alpha and CaM through a Ca2+-independent pathway.

KW - pancreatic ductal adenocarcinoma

KW - TRPC1

KW - cell proliferation

KW - spheroid growth

KW - cell cycle progression

KW - PI3K

KW - calmodulin

KW - CANONICAL 1 TRPC1

KW - CALCIUM-CHANNELS

KW - CANCER

KW - EXPRESSION

KW - CARCINOMA

KW - CALMODULIN

KW - MIGRATION

KW - GROWTH

KW - ENTRY

U2 - 10.3390/ijms23147923

DO - 10.3390/ijms23147923

M3 - Journal article

C2 - 35887266

VL - 23

JO - International Journal of Molecular Sciences (Online)

JF - International Journal of Molecular Sciences (Online)

SN - 1661-6596

IS - 14

M1 - 7923

ER -

ID: 316069920