Hyperpolyploidization of hepatocyte initiates preneoplastic lesion formation in the liver View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-01-28

AUTHORS

Heng Lin, Yen-Sung Huang, Jean-Michel Fustin, Masao Doi, Huatao Chen, Hui-Huang Lai, Shu-Hui Lin, Yen-Lurk Lee, Pei-Chih King, Hsien-San Hou, Hao-Wen Chen, Pei-Yun Young, Hsu-Wen Chao

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. More... »

PAGES

645

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-020-20572-8

DOI

http://dx.doi.org/10.1038/s41467-020-20572-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1134928281

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/33510150


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33 schema:description 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.
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40 CL region
41 HCC cells
42 abscission failure
43 accumulation
44 carcinoma
45 cells
46 centrilobular region
47 critical region
48 critical role
49 cytokinesis
50 development
51 diethylnitrosamine treatment
52 emergence
53 failure
54 foci formation
55 foci number
56 formation
57 genetic models
58 hepatocellular carcinoma
59 hepatocytes
60 hyperpolyploidization
61 increase
62 inhibition
63 lesion formation
64 link
65 liver
66 lobule
67 malignancy
68 midbody
69 model
70 molecular link
71 nucleus size
72 number
73 pharmacological inhibition
74 phosphorylation
75 predominant primary malignancy
76 preneoplastic lesion formation
77 primary malignancy
78 region
79 role
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82 treatment
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