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.

胆管癌（CCA）是一种特别具有侵略性的肝胆恶性肿瘤，其对恶性表型的潜在分子机制仍知之甚少，并且新颖有效的治疗策略受到限制。促生存蛋白激酶CK2在癌症中经常过度表达，并且作为抗肿瘤药物靶标越来越引起人们的关注。它在CCA生物学中的确切作用仍是未知之数。在这里，我们显示了在人CCA样品中CK2α和α'催化亚基以及β调节亚基的表达增加了。与未转化的胆管细胞相比，CCA细胞系中CK2亚基的表达增加。我们使用了对CK2的化学抑制和CRISPR / Cas9的基因修饰来研究CK2对CCA细胞恶性表型的贡献。CK2活性的破坏导致细胞通过凋亡死亡，减少的侵袭和迁移潜能以及G0 / G1细胞周期停滞。重要的是，CK2活性降低的CCA细胞对化疗更敏感。总而言之，我们的结果表明CK2显着有助于增加CCA细胞的增殖潜能和促进生长，并表明其靶向作为胆管癌的一种有前途的药理策略的理由。