The protein kinase CK2 contributes to the malignant phenotype of cholangiocarcinoma cells
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The protein kinase CK2 contributes to the malignant phenotype of cholangiocarcinoma cells. / Di Maira, Giovanni; Gentilini, Alessandra; Pastore, Mirella; Caligiuri, Alessandra; Piombanti, Benedetta; Raggi, Chiara; Rovida, Elisabetta; Lewinska, Monika; Andersen, Jesper B; Borgo, Christian; Salvi, Mauro; Ottaviani, Daniele; Ruzzene, Maria; Marra, Fabio.
In: Oncogenesis, Vol. 8, No. 11, 2019, p. 61-72.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The protein kinase CK2 contributes to the malignant phenotype of cholangiocarcinoma cells
AU - Di Maira, Giovanni
AU - Gentilini, Alessandra
AU - Pastore, Mirella
AU - Caligiuri, Alessandra
AU - Piombanti, Benedetta
AU - Raggi, Chiara
AU - Rovida, Elisabetta
AU - Lewinska, Monika
AU - Andersen, Jesper B
AU - Borgo, Christian
AU - Salvi, Mauro
AU - Ottaviani, Daniele
AU - Ruzzene, Maria
AU - Marra, Fabio
PY - 2019
Y1 - 2019
N2 - Cholangiocarcinoma (CCA) is a particularly aggressive hepatobiliary malignancy, for which the molecular mechanisms underlying the malignant phenotype are still poorly understood, and novel and effective therapeutic strategies are limited. The pro-survival protein kinase CK2 is frequently overexpressed in cancer and is receiving increasing interest as an anti-tumor drug target. Its precise role in CCA biology is still largely unknown. Here we show that expression of the CK2α and α' catalytic subunits and of the β regulatory subunit is increased in human CCA samples. Increased expression of CK2 subunits was shown in CCA cell lines compared to non-transformed cholangiocytes. We used chemical inhibition of CK2 and genetic modification by CRISPR/Cas9 to explore the contribution of CK2 to the malignant phenotype of CCA cells. Disruption of CK2 activity results in cell death through apoptosis, reduced invasion and migration potential, and G0/G1 cell cycle arrest. Importantly, CCA cells with a reduced CK2 activity are more sensitive to chemotherapy. Altogether, our results demonstrate that CK2 significantly contributes to increased proliferative potential and augmented growth of CCA cells and indicate the rationale for its targeting as a promising pharmacologic strategy for cholangiocarcinoma.
AB - Cholangiocarcinoma (CCA) is a particularly aggressive hepatobiliary malignancy, for which the molecular mechanisms underlying the malignant phenotype are still poorly understood, and novel and effective therapeutic strategies are limited. The pro-survival protein kinase CK2 is frequently overexpressed in cancer and is receiving increasing interest as an anti-tumor drug target. Its precise role in CCA biology is still largely unknown. Here we show that expression of the CK2α and α' catalytic subunits and of the β regulatory subunit is increased in human CCA samples. Increased expression of CK2 subunits was shown in CCA cell lines compared to non-transformed cholangiocytes. We used chemical inhibition of CK2 and genetic modification by CRISPR/Cas9 to explore the contribution of CK2 to the malignant phenotype of CCA cells. Disruption of CK2 activity results in cell death through apoptosis, reduced invasion and migration potential, and G0/G1 cell cycle arrest. Importantly, CCA cells with a reduced CK2 activity are more sensitive to chemotherapy. Altogether, our results demonstrate that CK2 significantly contributes to increased proliferative potential and augmented growth of CCA cells and indicate the rationale for its targeting as a promising pharmacologic strategy for cholangiocarcinoma.
U2 - 10.1038/s41389-019-0171-x
DO - 10.1038/s41389-019-0171-x
M3 - Journal article
C2 - 31641101
VL - 8
SP - 61
EP - 72
JO - Oncogenesis
JF - Oncogenesis
SN - 2157-9024
IS - 11
ER -
ID: 229268288