TY - JOUR TI - HDAC11 regulates glycolysis through the LKB1/AMPK signaling pathway to maintain hepatocellular carcinoma stemness AU - Bi, Lei AU - Ren, Yidan AU - Feng, Maoxiao AU - Meng, Peng AU - Wang, Qin AU - Chen, Weiping AU - Jiao, Qinlian AU - Wang, Yuli AU - Du, Lutao AU - Zhou, Fuqiong AU - Jiang, Yucui AU - Chen, Feiyan AU - Wang, Chuanxin AU - Tang, Bo AU - Wang, Yunshan T2 - Cancer Research AB - Hepatocellular carcinoma (HCC) contains a subset of cancer stem cells (CSC) that cause tumor recurrence, metastasis, and chemical resistance. Histone deacetylase 11 (HDAC11) mediates diverse immune functions and metabolism, yet little is known about its role in HCC CSCs. In this study, we report that HDAC11 is highly expressed in HCC and is closely related to disease prognosis. Depletion of HDAC11 in a conditional knockout (KO) mouse model reduced hepatocellular tumorigenesis and prolonged survival. Loss of HDAC11 increased transcription of LKB1 by promoting histone acetylation in its promoter region, thereby activating the AMPK signaling pathway and inhibiting the glycolysis pathway, which in turn leads to the suppression of cancer stemness and HCC progression. Furthermore, HDAC11 overexpression reduced HCC sensitivity to sorafenib. Collectively, these data propose HDAC11 as a new target for combination therapy in patients with kinase-resistant HCC. DA - 2021/01/01/ PY - 2021 DO - 10.1158/0008-5472.CAN-20-3044 DP - cancerres.aacrjournals.org J2 - Cancer Res LA - en SN - 0008-5472, 1538-7445 UR - https://cancerres.aacrjournals.org/content/early/2021/02/17/0008-5472.CAN-20-3044 Y2 - 2021/02/19/17:22:54 ER -