Abstract 2852: CITED2, an emerging regulator in hypoxia- and anoikis- mediated cancer cell growth

Abstract

Abstract In solid tumors, hypoxia and anoikis are two common phenomena occurred in the central of region, inducing a series of genes to switch metabolic pathways, prevent apoptosis and promote continuous growth of cancer cells. Herein, we reported that CITED2 (CBP/p300-interacting transactivators with glutamic acid (E)/aspartic acid (D)-rich C-terminal domain 2) responded to hypoxia and anoikis induction, preventing lung cancer cells from cell cycle arrest. We found that hypoxia induced CITED2 through a HIF2α dependent pathway; moreover, three-dimensional (3D) growth of lung cancer cells induced the expression of CITED2. 3D growth condition elicited anoikis-mediated cell cycle arrest, which was further potentiated by hypoxia stimulation. Knockdown of CITED2 or HIF2α in lung cancer cells enhanced anoikis, causing G1/S cell cycle arrest. Soft agar analysis displayed that both HIF2α and CITED2 are necessary for anchorage-independent cell growth under the hypoxic condition. Spheroid assay indicated that HIF2α-CITED2 signaling axis plays an important role in spheroid formation. Pearson correlation analysis showed that CITED2 was associated with HIF2α expression in lung adenocarcinoma. Kaplan Meier analysis revealed that CITED2 expression was correlated with poor survival outcomes in patients with lung adenocarcinoma. Thus, our findings support the notion that CITED2 plays a critical role in hypoxia- and anokis- mediated cancer cell growth with the potential as a prognostic biomarker for predicting lung cancer progression. Citation Format: Ming-Han Kuo, Chia Ee Chan, Yu-Ting Chou. CITED2, an emerging regulator in hypoxia- and anoikis- mediated cancer cell growth. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2852.