Nature communications, 2021-01, Vol.12 (1), p.645-18, Article 645
2021
Details
- Autor(en) / Beteiligte
- Titel
- Hyperpolyploidization of hepatocyte initiates preneoplastic lesion formation in the liver
- Ist Teil von
- Nature communications, 2021-01, Vol.12 (1), p.645-18, Article 645
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2021
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-020-20572-8Titel-ID: cdi_doaj_primary_oai_doaj_org_article_2a6b0a8610cd4b32b27ac9dde0bc48ce
- Format
- –
- Schlagworte
- Abscission, Accumulation, Animals, Carcinoma, Hepatocellular - chemically induced, Carcinoma, Hepatocellular - genetics, Carcinoma, Hepatocellular - metabolism, Cell Transformation, Neoplastic - chemically induced, Cell Transformation, Neoplastic - genetics, Cell Transformation, Neoplastic - metabolism, Cells, Cultured, Cytokinesis, Diethylnitrosamine, Diethylnitrosamine - toxicity, Female, Genetic transformation, Genotoxicity, Hepatocellular carcinoma, Hepatocytes, Hepatocytes - drug effects, Hepatocytes - metabolism, Humans, Liver, Liver - drug effects, Liver - metabolism, Liver - pathology, Liver cancer, Liver Neoplasms - chemically induced, Liver Neoplasms - genetics, Liver Neoplasms - metabolism, Male, Malignancy, Mice, Mice, Inbred C57BL, Mice, Inbred ICR, Mice, Inbred NOD, Mice, Knockout, Mice, SCID, Microscopy, Confocal, Phosphorylation, Polyploidy, Precancerous Conditions - chemically induced, Precancerous Conditions - genetics, Precancerous Conditions - metabolism, Tumors