Matches in SemOpenAlex for { <https://semopenalex.org/work/W2164938105> ?p ?o ?g. }
- W2164938105 endingPage "2849" @default.
- W2164938105 startingPage "2832" @default.
- W2164938105 abstract "Tumor-initiating stem-like cells (TICs) are resistant to chemotherapy and associated with hepatocellular carcinoma (HCC) caused by HCV and/or alcohol-related chronic liver injury. Using HCV Tg mouse models and patients with HCC, we isolated CD133(+) TICs and identified the pluripotency marker NANOG as a direct target of TLR4, which drives the tumor-initiating activity of TICs. These TLR4/NANOG-dependent TICs were defective in the TGF-β tumor suppressor pathway. Functional oncogene screening of a TIC cDNA library identified Yap1 and Igf2bp3 as NANOG-dependent genes that inactivate TGF-β signaling. Mechanistically, we determined that YAP1 mediates cytoplasmic retention of phosphorylated SMAD3 and suppresses SMAD3 phosphorylation/activation by the IGF2BP3/AKT/mTOR pathway. Silencing of both YAP1 and IGF2BP3 restored TGF-β signaling, inhibited pluripotency genes and tumorigenesis, and abrogated chemoresistance of TICs. Mice with defective TGF-β signaling (Spnb2(+/-) mice) exhibited enhanced liver TLR4 expression and developed HCC in a TLR4-dependent manner. Taken together, these results suggest that the activated TLR4/NANOG oncogenic pathway is linked to suppression of cytostatic TGF-β signaling and could potentially serve as a therapeutic target for HCV-related HCC." @default.
- W2164938105 created "2016-06-24" @default.
- W2164938105 creator A5001400839 @default.
- W2164938105 creator A5009910426 @default.
- W2164938105 creator A5015440896 @default.
- W2164938105 creator A5018278386 @default.
- W2164938105 creator A5033298543 @default.
- W2164938105 creator A5039882439 @default.
- W2164938105 creator A5040505921 @default.
- W2164938105 creator A5043932320 @default.
- W2164938105 creator A5057059496 @default.
- W2164938105 creator A5058204085 @default.
- W2164938105 creator A5065432765 @default.
- W2164938105 creator A5067147675 @default.
- W2164938105 date "2013-06-10" @default.
- W2164938105 modified "2023-10-10" @default.
- W2164938105 title "Reciprocal regulation by TLR4 and TGF-β in tumor-initiating stem-like cells" @default.
- W2164938105 cites W1529983307 @default.
- W2164938105 cites W1589761009 @default.
- W2164938105 cites W1633357948 @default.
- W2164938105 cites W1768438545 @default.
- W2164938105 cites W1963927300 @default.
- W2164938105 cites W1964317462 @default.
- W2164938105 cites W1970060716 @default.
- W2164938105 cites W1973346087 @default.
- W2164938105 cites W1975284118 @default.
- W2164938105 cites W1976637923 @default.
- W2164938105 cites W1976878409 @default.
- W2164938105 cites W1990324370 @default.
- W2164938105 cites W1991088949 @default.
- W2164938105 cites W1992506198 @default.
- W2164938105 cites W1996652335 @default.
- W2164938105 cites W1997508119 @default.
- W2164938105 cites W2001525581 @default.
- W2164938105 cites W2004452444 @default.
- W2164938105 cites W2011818472 @default.
- W2164938105 cites W2012141216 @default.
- W2164938105 cites W2019242560 @default.
- W2164938105 cites W2026211487 @default.
- W2164938105 cites W2026369900 @default.
- W2164938105 cites W2026428548 @default.
- W2164938105 cites W2029622854 @default.
- W2164938105 cites W2032924729 @default.
- W2164938105 cites W2037670359 @default.
- W2164938105 cites W2040618577 @default.
- W2164938105 cites W2046215345 @default.
- W2164938105 cites W2049792810 @default.
- W2164938105 cites W2053888540 @default.
- W2164938105 cites W2056992430 @default.
- W2164938105 cites W2057222323 @default.
- W2164938105 cites W2058093430 @default.
- W2164938105 cites W2058792197 @default.
- W2164938105 cites W2060772749 @default.
- W2164938105 cites W2064879069 @default.
- W2164938105 cites W2068424305 @default.
- W2164938105 cites W2073482890 @default.
- W2164938105 cites W2074079253 @default.
- W2164938105 cites W2074356752 @default.
- W2164938105 cites W2079560053 @default.
- W2164938105 cites W2082755434 @default.
- W2164938105 cites W2085543001 @default.
- W2164938105 cites W2086250583 @default.
- W2164938105 cites W2086549165 @default.
- W2164938105 cites W2092513068 @default.
- W2164938105 cites W2095455546 @default.
- W2164938105 cites W2101538557 @default.
- W2164938105 cites W2106787323 @default.
- W2164938105 cites W2107575419 @default.
- W2164938105 cites W2108447763 @default.
- W2164938105 cites W2109102339 @default.
- W2164938105 cites W2115585977 @default.
- W2164938105 cites W2117692326 @default.
- W2164938105 cites W2117720293 @default.
- W2164938105 cites W2118278569 @default.
- W2164938105 cites W2121507410 @default.
- W2164938105 cites W2123927899 @default.
- W2164938105 cites W2124528857 @default.
- W2164938105 cites W2127107445 @default.
- W2164938105 cites W2129788206 @default.
- W2164938105 cites W2132047377 @default.
- W2164938105 cites W2133835604 @default.
- W2164938105 cites W2134937820 @default.
- W2164938105 cites W2137672147 @default.
- W2164938105 cites W2140121036 @default.
- W2164938105 cites W2140254135 @default.
- W2164938105 cites W2140946995 @default.
- W2164938105 cites W2141002545 @default.
- W2164938105 cites W2141595533 @default.
- W2164938105 cites W2151220680 @default.
- W2164938105 cites W2151268204 @default.
- W2164938105 cites W2153060237 @default.
- W2164938105 cites W2158585862 @default.
- W2164938105 cites W2159376228 @default.
- W2164938105 cites W2167005345 @default.
- W2164938105 cites W2168472139 @default.
- W2164938105 cites W4254759378 @default.
- W2164938105 doi "https://doi.org/10.1172/jci65859" @default.
- W2164938105 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3696549" @default.