@article{f693fe1223f5478fa5b5642dd5badabe,
title = "Hyperpolyploidization of hepatocyte initiates preneoplastic lesion formation in the liver",
abstract = "Hepatocellular carcinoma (HCC) is the most predominant primary malignancy in the liver. Genotoxic and genetic models have revealed that HCC cells are derived from hepatocytes, but where the critical region for tumor foci emergence is and how this transformation occurs are still unclear. Here, hyperpolyploidization of hepatocytes around the centrilobular (CL) region is demonstrated to be closely linked with the development of HCC cells after diethylnitrosamine treatment. We identify the CL region as a dominant lobule for accumulation of hyperpolyploid hepatocytes and preneoplastic tumor foci formation. We also demonstrate that upregulation of Aurkb plays a critical role in promoting hyperpolyploidization. Increase of AURKB phosphorylation is detected on the midbody during cytokinesis, causing abscission failure and hyperpolyploidization. Pharmacological inhibition of AURKB dramatically reduces nucleus size and tumor foci number surrounding the CL region in diethylnitrosamine-treated liver. Our work reveals an intimate molecular link between pathological hyperpolyploidy of CL hepatocytes and transformation into HCC cells.",
author = "Heng Lin and Huang, {Yen Sung} and Fustin, {Jean Michel} and Masao Doi and Huatao Chen and Lai, {Hui Huang} and Lin, {Shu Hui} and Lee, {Yen Lurk} and King, {Pei Chih} and Hou, {Hsien San} and Chen, {Hao Wen} and Young, {Pei Yun} and Chao, {Hsu Wen}",
note = "Funding Information: The authors are indebted to Dr. Yi-Shuian Huang and Dr. Ruey-Bing Yang for supplying facilities and drugs for in vivo and in vitro studies. The authors thank the pathology core of Institute of Biomedical Sciences (IBMS) for paraffin blocks and H&E stain processing. The authors also thank the assistance from Ms. Tzu-Wen Tai and Ms. Chia-Chen Tai in the flow cytometry core facility of IBMS (AS-CFII108-113), Academia Sinica for analysis of flow cytometry. The authors are grateful to Mr. Kuan-Yu Chou and Ms. Show-Rong Ma in microscopes facility of IBMS for images acquisition. We thank Mr. Tsung-Hung Hung in Medical Art Room of IBMS for medical art construction. This work was supported by grants from the Taipei Medical University [105-5406-004-112], Ministry of Science and Technology of Taiwan [MoST108-2628-B-038-002 and MoST106-2320-B-038-026]. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
doi = "10.1038/s41467-020-20572-8",
language = "English",
volume = "12",
pages = "645",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Research",
number = "1",
}