リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「Hes1 is essential in proliferating ductal cell-mediated development of intrahepatic cholangiocarcinoma」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

Hes1 is essential in proliferating ductal cell-mediated development of intrahepatic cholangiocarcinoma

Matsumori, Tomoaki 京都大学 DOI:10.14989/doctor.k23369

2021.05.24

概要

Intrahepatic cholangiocarcinoma (ICC) is frequently driven by aberrant KRAS activation and develops in the liver with chronic inflammation. Although the Notch signaling pathway is critically involved in ICC development, detailed mechanisms of Notchdriven ICC development are still unknown. Here, we use mice whose Notch signaling is genetically engineered to show that the Notch signaling pathway, specifically the Notch/Hes1 axis, plays an essential role in expanding ductular cells in the liver with chronic inflammation or oncogenic Kras activation. Activation of Notch1 enhanced the development of proliferating ductal cells (PDC) in injured livers, while depletion of Hes1 led to suppression. In correlation with PDC expansion, ICC development was also regulated by the Notch/Hes1 axis and suppressed by Hes1 depletion. Lineage-tracing experiments using EpcamcreERT2 mice further confirmed that Hes1 plays a critical role in the induction of PDC and that ICC could originate from PDC. Analysis of human ICC specimens showed PDC in nonneoplastic background tissues, confirming HES1 expression in both PDC and ICC tumor cells. Our findings provide novel direct experimental evidence that Hes1 plays an essential role in the development of ICC via PDC.

この論文で使われている画像

参考文献

1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69–90.

2. Thinkhamrop K, Khuntikeo N, Phonjitt P, Chamadol N, Thinkhamrop B, Moore MA, et al. Association between diabetes mellitus and fatty liver based on ultrasonography screening in the world’s highest cholangiocarcinoma incidence region, Northeast Thailand. Asian Pac J Cancer Prev 2015;16: 3931–6.

3. Navas MC, Glaser S, Dhruv H, Celinski S, Alpini G, Meng F. Hepatitis C virus infection and cholangiocarcinoma: an insight into epidemiologic evidences and hypothetical mechanisms of oncogenesis. Am J Pathol 2019;189:1122–32.

4. Zhang H, Yang T, Wu M, Shen F. Intrahepatic cholangiocarcinoma: epidemiology, risk factors, diagnosis and surgical management. Cancer Lett 2016;379: 198–205.

5. Chiba T, Marusawa H, Ushijima T. Inflammation-associated cancer development in digestive organs: mechanisms and roles for genetic and epigenetic modulation. Gastroenterology 2012;143:550–63.

6. Nakamura H, Arai Y, Totoki Y, Shirota T, Elzawahry A, Kato M, et al. Genomic spectra of biliary tract cancer. Nat Genet 2015;47:1003–10.

7. Schulze K, Imbeaud S, Letouze E, Alexandrov LB, Calderaro J, Rebouissou S, et al. Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets. Nat Genet 2015;47:505–11.

8. Guest RV, Boulter L, Kendall TJ, Minnis-Lyons SE, Walker R, Wigmore SJ, et al. Cell lineage tracing reveals a biliary origin of intrahepatic cholangiocarcinoma. Cancer Res 2014;74:1005–10.

9. O’Dell MR, Huang JL, Whitney-Miller CL, Deshpande V, Rothberg P, Grose V, et al. Kras(G12D) and p53 mutation cause primary intrahepatic cholangiocarcinoma. Cancer Res 2012;72:1557–67.

10. Hill MA, Alexander WB, Guo B, Kato Y, Patra KC, O’Dell MR, et al. Kras and Tp53 mutations cause cholangiocyte- and hepatocyte-derived cholangiocarcinoma. Cancer Res 2018;78:4445–51.

11. Geisler F, Strazzabosco M. Emerging roles of Notch signaling in liver disease. Hepatology 2015;61:382–92.

12. Kodama Y, Hijikata M, Kageyama R, Shimotohno K, Chiba T. The role of notch signaling in the development of intrahepatic bile ducts. Gastroenterology 2004; 127:1775–86.

13. Huntzicker EG, Hotzel K, Choy L, Che L, Ross J, Pau G, et al. Differential effects of targeting Notch receptors in a mouse model of liver cancer. Hepatology 2015; 61:942–52.

14. Zhang S, Wang J, Wang H, Fan L, Fan B, Zeng B, et al. Hippo cascade controls lineage commitment of liver tumors in mice and humans. Am J Pathol 2018;188: 995–1006.

15. Wang J, Dong M, Xu Z, Song X, Zhang S, Qiao Y, et al. Notch2 controls hepatocyte-derived cholangiocarcinoma formation in mice. Oncogene 2018;37: 3229–42.

16. Zender S, Nickeleit I, Wuestefeld T, Sorensen I, Dauch D, Bozko P, et al. A critical role for notch signaling in the formation of cholangiocellular carcinomas. Cancer Cell 2013;23:784–95.

17. Guest RV, Boulter L, Dwyer BJ, Kendall TJ, Man TY, Minnis-Lyons SE, et al. Notch3 drives development and progression of cholangiocarcinoma. Proc Natl Acad Sci U S A 2016;113:12250–5.

18. Villanueva A, Alsinet C, Yanger K, Hoshida Y, Zong Y, Toffanin S, et al. Notch signaling is activated in human hepatocellular carcinoma and induces tumor formation in mice. Gastroenterology 2012;143:1660–9.

19. Gao J, Xiong Y, Wang Y, Wang Y, Zheng G, Xu H. Hepatitis B virus X protein activates Notch signaling by its effects on Notch1 and Notch4 in human hepatocellular carcinoma. Int J Oncol 2016;48:329–37.

20. Perron A, Nishikawa Y, Iwata J, Shimojo H, Takaya J, Kobayashi K, et al. Smallmolecule screening yields a compound that inhibits the cancer-associated transcription factor Hes1 via the PHB2 chaperone. J Biol Chem 2018;293: 8285–94.

21. Arai MA, Ishikawa N, Tanaka M, Uemura K, Sugimitsu N, Suganami A, et al. Hes1 inhibitor isolated by target protein oriented natural products isolation (TPO-NAPI) of differentiation activators of neural stem cells. Chem Sci 2016;7: 1514–20.

22. Sia D, Villanueva A, Friedman SL, Llovet JM. Liver cancer cell of origin, molecular class, and effects on patient prognosis. Gastroenterology 2017;152: 745–61.

23. Fan B, Malato Y, Calvisi DF, Naqvi S, Razumilava N, Ribback S, et al. Cholangiocarcinomas can originate from hepatocytes in mice. J Clin Invest 2012;122:2911–5.

24. Jors S, Jeliazkova P, Ringelhan M, Thalhammer J, Durl S, Ferrer J, et al. Lineage fate of ductular reactions in liver injury and carcinogenesis. J Clin Invest 2015; 125:2445–57.

25. Miyajima A, Tanaka M, Itoh T. Stem/progenitor cells in liver development, homeostasis, regeneration, and reprogramming. Cell Stem Cell 2014;14: 561–74.

26. Shin S, Upadhyay N, Greenbaum LE, Kaestner KH. Ablation of Foxl1-Crelabeled hepatic progenitor cells and their descendants impairs recovery of mice from liver injury. Gastroenterology 2015;148:192–202.

27. Miura Y, Matsui S, Miyata N, Harada K, Kikkawa Y, Ohmuraya M, et al. Differential expression of Lutheran/BCAM regulates biliary tissue remodeling in ductular reaction during liver regeneration. eLife 2018;7:e36572.

28. Matsumoto T, Takai A, Eso Y, Kinoshita K, Manabe T, Seno H, et al. Proliferating EpCAM-positive ductal cells in the inflamed liver give rise to hepatocellular carcinoma. Cancer Res 2017;77:6131–43.

29. Boulter L, Govaere O, Bird TG, Radulescu S, Ramachandran P, Pellicoro A, et al. Macrophage-derived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease. Nat Med 2012;18:572–9.

30. Eso Y, Takai A, Matsumoto T, Inuzuka T, Horie T, Ono K, et al. MSH2 dysregulation is triggered by proinflammatory cytokine stimulation and is associated with liver cancer development. Cancer Res 2016;76: 4383–93.

31. Imayoshi I, Shimogori T, Ohtsuka T, Kageyama R. Hes genes and neurogenin regulate non-neural versus neural fate specification in the dorsal telencephalic midline. Development 2008;135:2531–41.

32. Jackson EL, Willis N, Mercer K, Bronson RT, Crowley D, Montoya R, et al. Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev 2001;15:3243–8.

33. Olive KP, Tuveson DA, Ruhe ZC, Yin B, Willis NA, Bronson RT, et al. Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome. Cell 2004; 119:847–60.

34. Madisen L, Zwingman TA, Sunkin SM, Oh SW, Zariwala HA, Gu H, et al. A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat Neurosci 2009;13:133–40.

35. Murtaugh LC, Stanger BZ, Kwan KM, Melton DA. Notch signaling controls multiple steps of pancreatic differentiation. Proc Natl Acad Sci U S A 2003;100: 14920–5.

36. Ito T, Udaka N, Yazawa T, Okudela K, Hayashi H, Sudo T, et al. Basic helix-loop-helix transcription factors regulate the neuroendocrine differentiation of fetal mouse pulmonary epithelium. Development 2000; 127:3913–21.

37. Okabe M, Tsukahara Y, Tanaka M, Suzuki K, Saito S, Kamiya Y, et al. Potential hepatic stem cells reside in EpCAMþ cells of normal and injured mouse liver. Development 2009;136:1951–60.

38. Yamashita T, Wang XW. Cancer stem cells in the development of liver cancer. J Clin Invest 2013;123:1911–8.

39. O’Rourke CJ, Matter MS, Nepal C, Caetano-Oliveira R, Ton PT, Factor VM, et al. Identification of a pan-gamma-secretase inhibitor response signature for Notch-driven cholangiocarcinoma. Hepatology 2020;71: 196–213.

40. Hidalgo-Sastre A, Brodylo RL, Lubeseder-Martellato C, Sipos B, Steiger K, Lee M, et al. Hes1 controls exocrine cell plasticity and restricts development of pancreatic ductal adenocarcinoma in a mouse model. Am J Pathol 2016;186: 2934–44.

41. Nishikawa Y, Kodama Y, Shiokawa M, Matsumori T, Marui S, Kuriyama K, et al. Hes1 plays an essential role in Kras-driven pancreatic tumorigenesis. Oncogene 2019;38:4283–96.

42. Cheong JK, Zhang F, Chua PJ, Bay BH, Thorburn A, Virshup DM. Casein kinase 1alpha-dependent feedback loop controls autophagy in RAS-driven cancers. J Clin Invest 2015;125:1401–18.

43. Kent LN, Leone G. The broken cycle: E2F dysfunction in cancer. Nat Rev Cancer 2019;19:326–38.

44. Jeliazkova P, Jors S, Lee M, Zimber-Strobl U, Ferrer J, Schmid RM, et al. Canonical Notch2 signaling determines biliary cell fates of embryonic hepatoblasts and adult hepatocytes independent of Hes1. Hepatology 2013;57:2469–79.

45. Aoki S, Mizuma M, Takahashi Y, Haji Y, Okada R, Abe T, et al. Aberrant activation of Notch signaling in extrahepatic cholangiocarcinoma: clinicopathological features and therapeutic potential for cancer stem cell-like properties. BMC Cancer 2016;16:854.

46. Chung WC, Wang J, Zhou Y, Xu K. Kras(G12D) upregulates Notch signaling to induce gallbladder tumorigenesis in mice. Oncoscience 2017;4:131–8.

47. Holczbauer A, Factor VM, Andersen JB, Marquardt JU, Kleiner DE, Raggi C, et al. Modeling pathogenesis of primary liver cancer in lineage-specific mouse cell types. Gastroenterology 2013;145:221–31.

48. Kawaguchi Y. Sox9 and programming of liver and pancreatic progenitors. J Clin Invest 2013;123:1881–6.

49. Andersson ER, Lendahl U. Therapeutic modulation of Notch signalling–are we there yet? Nat Rev Drug Discov 2014;13:357–78.

50. Doody RS, Raman R, Sperling RA, Seimers E, Sethuraman G, Mohs R, et al. Peripheral and central effects of gamma-secretase inhibition by semagacestat in Alzheimer’s disease. Alzheimers Res Ther 2015;7:36.

参考文献をもっと見る

全国の大学の
卒論・修論・学位論文

一発検索!

この論文の関連論文を見る