Wen Yang;He Xin Yan;Lei Chen;Qiong Liu;Ya Qin He;Le Xing Yu;Shu Hui Zhang;Dan Dan Huang;Liang Tang;Xiao Ni Kong;Chao Chen;Shu Qin Liu;孟超 吴;红阳 王
Second Military Medical University;Shanghai Jiao Tong University
发表时间:2008-6-1
期 刊:Cancer Research
语 言:English
U R L: http://www.scopus.com/inward/record.url?scp=49249122615&partnerID=8YFLogxK
Adult hepatic progenitor (oval) cells are facultative stem cells in liver, which participate in a range of human liver diseases, including hepatocellular carcinoma (HCC). However, the molecular pathways regulating the expansion and differentiation of these cells are poorly understood. We show that active Wnt/β-catenin signaling occurs preferentially within the oval cell population, and forced expression of constitutively active β-catenin mutant promotes expansion of the oval cell population in the regenerated liver. More importantly, we identify a subpopulation of less differentiated progenitor-like cells in HCC cell lines and primary HCC tissues, which are defined by expression of the hepatic progenitor marker OV6 and endowed with endogenously active Wnt/β-catenin signaling. These OV6+ HCC cells possess a greater ability to form tumor in vivo and show a substantial resistance to standard chemotherapy compared with OV6- tumor cells. The fraction of tumor cells expressing OV6 is enriched after Wnt pathway activation, whereas inhibition of β-catenin signaling leads to a decrease in the proportion of OV6+ cells. In addition, the chemoresistance of OV6+ HCC progenitor-like cells can be reversed by lentivirus-delivered stable expression of micro-RNA targeting β-catenin. These results highlight the importance of the Wnt/β-catenin pathway in activation and expansion of oval cells in normal rodent models and human HCCs. OV6+ tumor cells may represent the cellular population that confers HCC chemoresistance, and therapies targeted to the Wnt/β-catenin signaling may provide a specific method to disrupt this resistance mechanism to improve overall tumor control with chemotherapy.
Scopus度量
年份 | CiteScore | SJR | SNIP |
---|---|---|---|
1996 | |||
1997 | |||
1998 | |||
1999 | 4.76 | 2.201 | |
2000 | 4.564 | 2.066 | |
2001 | 4.432 | 2.007 | |
2002 | 4.409 | 1.836 | |
2003 | 4.505 | 1.946 | |
2004 | 4.297 | 1.88 | |
2005 | 4.503 | 1.806 | |
2006 | 4.517 | 1.756 | |
2007 | 5.09 | 1.767 | |
2008 | 5.296 | 1.752 | |
2009 | 5.294 | 1.802 | |
2010 | 5.435 | 1.803 | |
2011 | 15.2 | 5.35 | 1.828 |
2012 | 16.7 | 5.076 | 2.018 |
2013 | 17.2 | 5.676 | 2.093 |
2014 | 15.9 | 5.683 | 2.074 |
2015 | 16.2 | 5.358 | 2.025 |
2016 | 15.5 | 4.908 | 1.999 |
2017 | 13.8 | 4.26 | 1.718 |
2018 | 12.9 | 4.047 | 1.637 |
2019 | 13.5 | 4.051 | 1.795 |
2020 | 15.8 | 4.103 | 1.983 |
2021 | 13.1 |
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