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

Girault, Alban; Rybarczyk, Pierre; Telliez, Marie-Sophie; Guénin, Stéphanie; Tebbakha, Riad; Sevestre, Henri; Ahidouch, Ahmed; Pedersen, Stine Falsig; Ouadid-Ahidouch, Halima; Schnipper, Julie; Kouba, Sana; Hague, Frédéric

doi:10.3390/ijms23147923

Cited by 5 publications

(22 citation statements)

References 65 publications

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“…Cells were transfected with small interfering RNA (siRNA) by electroporation using nucleofection (Amaxa Biosystems, Lonza, Aubergenville, France) as previously described [37]. Briefly, PANC-1 cells (1 × 10 6 ) grown under either normal pH, acid adaptation, or acid recovery conditions, were transiently nucleofected according to the manufacturer's protocol.…”

Section: Transient Transfectionsmentioning

confidence: 99%

“…The 6 × 10 5 non-transfected or 1 × 10 6 transfected PANC-1 cells grown in the three different pH conditions were seeded in 10 cm Petri dishes and collected after 72 h. As previously described [37], 500 µg of proteins were used for co-immunoprecipitation with SureBeads™ Protein A Magnetic Beads (Bio-Rad, France). Beads were washed thoroughly, according to the manufacturer's protocol.…”

Section: Co-immunoprecipitationmentioning

confidence: 99%

“…The 8 × 10 4 non-transfected PANC-1 cells, grown under the three different pH conditions, were seeded on coverslips for 48 h. Immunofluorescent staining was performed as previously described [37]. Briefly, cells were washed in cold PBS and fixed for 20 min at room temperature in 4% paraformaldehyde (PFA, Sigma, Saint-Quentin-Fallavier, France).…”

Section: Immunofluorescence Assay and Analysismentioning

confidence: 99%

“…Proliferation was calculated as the total number of viable cells (alive/white cells) normalized to the control. As previously described, we tested the effect of extracellular Ca 2+ concentrations on proliferation [37]. Here, the same counting procedure as described above was carried out, but after 24 h of seeding, the medium was changed to medium with standard conditions containing 1 mM Ca 2+ (referred to as conditions with Ca 2+ ) or containing EGTA to chelate Ca 2+ and to end with a final concentration of 30 µM (referred to conditions without Ca 2+ ).…”

Section: Trypan Blue Assaymentioning

confidence: 99%

“…We have recently shown that TRPC1 is overexpressed in PDAC tissue and cell lines but does not regulate either basal Ca 2+ entry or store-operated Ca 2+ entry (SOCE). However, TRPC1 regulates PANC-1 cell proliferation by interacting with phosphoinositol-3-kinase (PI3K) and calmodulin (CaM) and regulating AKT signaling in normal pH conditions [37].…”

Section: Introductionmentioning

confidence: 99%

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Acid Adaptation Promotes TRPC1 Plasma Membrane Localization Leading to Pancreatic Ductal Adenocarcinoma Cell Proliferation and Migration through Ca2+ Entry and Interaction with PI3K/CaM

Schnipper

Kouba

Hague

et al. 2022

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with a low overall survival rate of less than 10% and limited therapeutic options. Fluctuations in tumor microenvironment pH are a hallmark of PDAC development and progression. Many ion channels are bona fide cellular sensors of changes in pH. Yet, the interplay between the acidic tumor microenvironment and ion channel regulation in PDAC is poorly understood. In this study, we show that acid adaption increases PANC-1 cell migration but attenuates proliferation and spheroid growth, which are restored upon recovery. Moreover, acid adaptation and recovery conditions favor the plasma membrane localization of the pH-sensitive calcium (Ca2+) channel transient receptor potential C1 (TRPC1), TRPC1-mediated Ca2+ influx, channel interaction with the PI3K p85α subunit and calmodulin (CaM), and AKT and ERK1/2 activation. Knockdown (KD) of TRPC1 suppresses cell migration, proliferation, and spheroid growth, notably in acid-recovered cells. KD of TRPC1 causes the accumulation of cells in G0/G1 and G2/M phases, along with reduced expression of CDK6, −2, and −1, and cyclin A, and increased expression of p21CIP1. TRPC1 silencing decreases the basal Ca2+ influx in acid-adapted and -recovered cells, but not in normal pH conditions, and Ca2+ chelation reduces cell migration and proliferation solely in acid adaptation and recovery conditions. In conclusion, acid adaptation and recovery reinforce the involvement of TRPC1 in migration, proliferation, and cell cycle progression by permitting Ca2+ entry and forming a complex with the PI3K p85α subunit and CaM.

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Section: Transient Transfectionsmentioning

confidence: 99%

Section: Co-immunoprecipitationmentioning

confidence: 99%

Section: Immunofluorescence Assay and Analysismentioning

confidence: 99%

Section: Trypan Blue Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Acid Adaptation Promotes TRPC1 Plasma Membrane Localization Leading to Pancreatic Ductal Adenocarcinoma Cell Proliferation and Migration through Ca2+ Entry and Interaction with PI3K/CaM

Schnipper

Kouba

Hague

et al. 2022

Cancers

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SKF96365 Inhibits Tumor Proliferation by Inducing Apoptosis and Autophagy in Human Esophageal Squamous Cell Carcinoma

Zhang,

Han,

Liu

et al. 2024

International Journal of Genomics

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Calcium channel blockers are emerging as a new generation of attractive anticancer drugs. SKF96365, originally thought to be a store‐operated calcium entry (SOCE) inhibitor, is now often used as a TRPC channel blocker and is widely used in medical diagnostics. SKF96365 has shown antitumor effects on a variety of cancer cell lines. The objective of this study was to investigate the anticancer effect of SKF96365 on esophageal cancer in vivo and in vitro. Cell Counting Kit‐8 (CCK‐8) and colony formation were used to test the proliferation inhibition of SKF96365 on cell lines. Western blot and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to detect cell apoptosis rates. In addition, we demonstrated the antitumor effect of SKF96365 in vivo in xenografted mice. As a result, SKF96365 significantly inhibited the proliferation of K510, K30, and EC9706 in vitro. SKF96365 induces apoptosis in three cell lines through the poly(adenosine diphosphate–ribose) polymerase (PARP), caspase‐9, and BCL‐2 pathways in a dose‐dependent and time‐dependent manner. Moreover, SKF96365 treatment also induced apoptosis and inhibited tumor growth in nude mice. The calcium channel TRPC1 was significantly downregulated by SKF96365. Autophagy was also induced during the treatment of SKF96365. In summary, SKF96365 induces apoptosis (PARP, caspase‐9, and BCL‐2) and autophagy (LC3‐A/B) by inhibiting TRPC1 in esophageal cancer cells, thereby inhibiting tumor growth.

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Transient receptor potential channels’ genes forecast cervical cancer outcomes and illuminate its impact on tumor cells

Jiang,

Lin,

et al. 2024

Front. Genet.

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Introduction: In recent years, there has been a strong association between transient receptor potential (TRP) channels and the development of various malignancies, drug resistance, and resistance to radiotherapy. Consequently, we have investigated the relationship between transient receptor potential channels and cervical cancer from multiple angles.Methods: Patients’ mRNA expression profiles and gene variants were obtained from the TCGA database. Key genes in transient receptor potential channel prognosis-related genes (TRGs) were screened using the least absolute shrinkage and selection operator (LASSO) regression method, and a risk signature was constructed based on the expression of key genes. Various analyses were performed to evaluate the prognostic significance, biological functions, immune infiltration, and response to immunotherapy based on the risk signature.Results: Our research reveals substantial differences between high and low-risk groups in prognosis, tumor microenvironment, tumor mutational load, immune infiltration, and response to immunotherapy. Patients in the high-risk group exhibited poorer prognosis, lower tumor microenvironment scores and reduced response to immunotherapy while showing increased sensitivity to specific targeted drugs. In vitro experiments further illustrated that inhibiting transient receptor potential channels effectively decreased the proliferation, invasion, and migration of cervical cancer cells.Discussion: This study highlights the significant potential of transient receptor potential channels in cervical cancer, emphasizing their crucial role in prognostic prediction and personalized treatment strategies. The combination of TRP inhibitors with immunotherapy and targeted drugs may offer promise for individuals affected by cervical cancer.

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

Cited by 5 publications

References 65 publications

Acid Adaptation Promotes TRPC1 Plasma Membrane Localization Leading to Pancreatic Ductal Adenocarcinoma Cell Proliferation and Migration through Ca2+ Entry and Interaction with PI3K/CaM

Acid Adaptation Promotes TRPC1 Plasma Membrane Localization Leading to Pancreatic Ductal Adenocarcinoma Cell Proliferation and Migration through Ca2+ Entry and Interaction with PI3K/CaM

SKF96365 Inhibits Tumor Proliferation by Inducing Apoptosis and Autophagy in Human Esophageal Squamous Cell Carcinoma

Transient receptor potential channels’ genes forecast cervical cancer outcomes and illuminate its impact on tumor cells

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