Overexpression of hepatocyte nuclear factor 4α in human mesenchymal stem cells suppresses hepatocellular carcinoma development through Wnt/β-catenin signaling pathway downregulation

Cancer Biology and Therapy

Volumn 17, Issue 5, 2016, Pages 558-565

  Wu, Ning ^a,b   Zhang, Yu Ling ^c   Wang, Hai Tian ^b   Li, Da Wei ^a   Dai, Hui Juan ^a   Zhang, Qi Qi ^a   Zhang, Jiang ^a   Ma, Yong ^b   Xia, Qiang ^a   Bian, Jian Min ^b   Hang, Hua Lian ^a  

^a SHANGHAI JIAO TONG UNIVERSITY SCHOOL OF MEDICINE   (China)

^b NANJING MEDICAL UNIVERSITY   (China)

^c ZUNYI MEDICAL UNIVERSITY   (China)

Author keywords

Gene therapy; hepatocyte nuclear factor 4 ; hepatoma; mesenchymal stem cells; Wnt catenin signaling

Indexed keywords

BETA CATENIN; CYCLIN D1; GELATINASE A; GELATINASE B; HEPATOCYTE NUCLEAR FACTOR 4ALPHA; MYC PROTEIN; HEPATOCYTE NUCLEAR FACTOR;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER GROWTH; CELL INVASION; CELL PROLIFERATION; CONDITIONED MEDIUM; CONTROLLED STUDY; DOWN REGULATION; GENE OVEREXPRESSION; HEPATOMA CELL; HUMAN; HUMAN CELL; IMMUNOBLOTTING; IN VITRO STUDY; IN VIVO STUDY; LIVER CARCINOGENESIS; LIVER CELL CARCINOMA; MESENCHYMAL STEM CELL; METASTASIS; STABLE TRANSFECTION; UMBILICAL CORD; WNT SIGNALING PATHWAY; ANIMAL; GENETIC TRANSFECTION; GENETICS; LIVER TUMOR; MALE; MESENCHYMAL STROMA CELL; METABOLISM; MOUSE; NUDE MOUSE; PATHOLOGY; WNT SIGNALING;

ANIMALS; CARCINOMA, HEPATOCELLULAR; CELL PROLIFERATION; DOWN-REGULATION; HEPATOCYTE NUCLEAR FACTORS; HUMANS; LIVER NEOPLASMS; MALE; MESENCHYMAL STROMAL CELLS; MICE; MICE, NUDE; TRANSFECTION; WNT SIGNALING PATHWAY;

EID: 84969245584     PISSN: 15384047     EISSN: 15558576     Source Type: Journal    
DOI: 10.1080/15384047.2016.1177675     Document Type: Article

References (34)

1. C.D.Porada, G.Almeida-Porada. Mesenchymal stem cells as therapeutics and vehicles for gene and drug delivery. Adv Drug Deliv Rev 2010; 62:1156-66; PMID:20828588; http://dx.doi.org/10.1016/j.addr.2010.08.010
2. A.DeLaForest, M.Nagaoka, K.Si-Tayeb, F.K.Noto, G.Konopka, M.A.Battle, S.A.Duncan. HNF4A is essential for specification of hepatic progenitors from human pluripotent stem cells. Development 2011; 138:4143-53; PMID:21852396; http://dx.doi.org/10.1242/dev.062547
3. T.Tanaka, S.Jiang, H.Hotta, K.Takano, H.Iwanari, K.Sumi, K.Daigo, R.Ohashi, M.Sugai, C.Ikegame, et al. Dysregulated expression of P1 and P2 promoter-driven hepatocyte nuclear factor-4alpha in the pathogenesis of human cancer. J Pathol 2006; 208:662-72; PMID:16400631; http://dx.doi.org/10.1002/path.1928
4. H.Hang, Y.Yu, N.Wu, Q.Huang, Q.Xia, J.Bian. Induction of highly functional hepatocytes from human umbilical cord mesenchymal stem cells by HNF4alpha transduction. PloS one 2014; 9:e104133; PMID:25137413; http://dx.doi.org/10.1371/journal.pone.0104133
5. J.M.Llovet, A.Burroughs, J.Bruix. Hepatocellular carcinoma. The Lancet 2003; 362:1907-17; PMID:14667750; http://dx.doi.org/10.1016/S0140-6736(03)14964-1
6. N.Portolani, A.Coniglio, S.Ghidoni, M.Giovanelli, A.Benetti, G.A.Tiberio, S.M.Giulini. Early and late recurrence after liver resection for hepatocellular carcinoma: prognostic and therapeutic implications. Annal Surg 2006; 243:229-35; PMID:16432356; http://dx.doi.org/10.1097/01.sla.0000197706.21803.a1
7. J.Bayo, M.Marrodan, J.B.Aquino, M.Silva, M.G.Garcia, G.Mazzolini. The therapeutic potential of bone marrow-derived mesenchymal stromal cells on hepatocellular carcinoma. Liver Int 2014; 34:330-42; PMID:24112437; http://dx.doi.org/10.1111/liv.12338
8. A.Mantovani, P.Allavena, A.Sica, F.Balkwill. Cancer-related inflammation. Nature 2008; 454:436-44; PMID:18650914; http://dx.doi.org/10.1038/nature07205
9. A.Can, S.Karahuseyinoglu. Concise review: human umbilical cord stroma with regard to the source of fetus-derived stem cells. Stem cells 2007; 25:2886-95; PMID:17690177; http://dx.doi.org/10.1634/stemcells.2007-0417
10. S.H.Koh, K.S.Kim, M.R.Choi, K.H.Jung, K.S.Park, Y.G.Chai, W.Roh, S.J.Hwang, H.J.Ko, Y.M.Huh, et al. Implantation of human umbilical cord-derived mesenchymal stem cells as a neuroprotective therapy for ischemic stroke in rats. Brain Res 2008; 1229:233-48; PMID:18634757; http://dx.doi.org/10.1016/j.brainres.2008.06.087
11. T.Saandi, F.Baraille, L.Derbal-Wolfrom, A.L.Cattin, F.Benahmed, E.Martin, P.Cardot, B.Duclos, A.Ribeiro, J.N.Freund, et al. Regulation of the tumor suppressor homeogene Cdx2 by HNF4alpha in intestinal cancer. Oncogene 2013; 32:3782-8; PMID:22986531; http://dx.doi.org/10.1038/onc.2012.401
12. B.F.Ning, J.Ding, J.Liu, C.Yin, W.P.Xu, W.M.Cong, Q.Zhang, F.Chen, T.Han, X.Deng, et al. Hepatocyte nuclear factor 4alpha-nuclear factor-kappaB feedback circuit modulates liver cancer progression. Hepatology 2014; 60:1607-19; PMID:24752868; http://dx.doi.org/10.1002/hep.27177
13. B.F.Ning, J.Ding, C.Yin, W.Zhong, K.Wu, X.Zeng, W.Yang, Y.X.Chen, J.P.Zhang, X.Zhang, et al. Hepatocyte nuclear factor 4 alpha suppresses the development of hepatocellular carcinoma. Cancer Res 2010; 70:7640-51; PMID:20876809; http://dx.doi.org/10.1158/0008-5472.CAN-10-0824
14. M.Hatziapostolou, C.Polytarchou, E.Aggelidou, A.Drakaki, G.A.Poultsides, S.A.Jaeger, H.Ogata, M.Karin, K.Struhl, M.Hadzopoulou-Cladaras, et al. An HNF4alpha-miRNA inflammatory feedback circuit regulates hepatocellular oncogenesis. Cell 2011; 147:1233-47; PMID:22153071; http://dx.doi.org/10.1016/j.cell.2011.10.043
15. C.P.Hodgkinson, J.A.Gomez, M.Mirotsou, V.J.Dzau. Genetic engineering of mesenchymal stem cells and its application in human disease therapy. Hum Gene Ther 2010; 21:1513-26; PMID:20825283; http://dx.doi.org/10.1089/hum.2010.165
16. S.Kidd, E.Spaeth, A.Klopp, M.Andreeff, B.Hall, F.C.Marini. The (in) auspicious role of mesenchymal stromal cells in cancer: be it friend or foe. Cytotherapy 2008; 10:657-67; PMID:18985472; http://dx.doi.org/10.1080/14653240802486517
17. L.Kucerova, V.Altanerova, M.Matuskova, S.Tyciakova, C.Altaner. Adipose tissue-derived human mesenchymal stem cells mediated prodrug cancer gene therapy. Cancer Res 2007; 67:6304-13; PMID:17616689; http://dx.doi.org/10.1158/0008-5472.CAN-06-4024
18. C.Yin, Y.Lin, X.Zhang, Y.X.Chen, X.Zeng, H.Y.Yue, J.L.Hou, X.Deng, J.P.Zhang, Z.G.Han, et al. Differentiation therapy of hepatocellular carcinoma in mice with recombinant adenovirus carrying hepatocyte nuclear factor-4alpha gene. Hepatology 2008; 48:1528-39; PMID:18925631; http://dx.doi.org/10.1002/hep.22510
19. C.L.Hall, A.Bafico, J.Dai, S.A.Aaronson, E.T.Keller. Prostate cancer cells promote osteoblastic bone metastases through Wnts. Cancer research 2005; 65:7554-60; PMID:16140917; http://dx.doi.org/10.1158/0008-5472.CAN-05-1317
20. J.M.Gonzalez-Sancho, O.Aguilera, J.M.Garcia, N.Pendas-Franco, C.Pena, S.Cal, A.Garcia de Herreros, F.Bonilla, A.Munoz. The Wnt antagonist DICKKOPF-1 gene is a downstream target of beta-catenin/TCF and is downregulated in human colon cancer. Oncogene 2005; 24:1098-103; PMID:15592505; http://dx.doi.org/10.1038/sj.onc.1208303
21. K.Kozinski, A.Dobrzyn. [Wnt signaling pathway–its role in regulation of cell metabolism]. Postepy Hig Med Dosw 2013; 67:1098-108; PMID:24379251; http://dx.doi.org/10.5604/17322693.1077719
22. G.X.Jiang, W.Liu, Y.F.Cui, X.Y.Zhong, S.Tai, Z.D.Wang, Y.G.Shi, C.L.Li, S.Y.Zhao. Reconstitution of secreted frizzled-related protein 1 suppresses tumor growth and lung metastasis in an orthotopic model of hepatocellular carcinoma. Digest Dis Sci 2010; 55:2838-43; PMID:20033841; http://dx.doi.org/10.1007/s10620-009-1099-3
23. C.L.Huang, D.Liu, S.Ishikawa, T.Nakashima, N.Nakashima, H.Yokomise, K.Kadota, M.Ueno. Wnt1 overexpression promotes tumour progression in non-small cell lung cancer. Eur J Cancer 2008; 44:2680-8; PMID:18790633; http://dx.doi.org/10.1016/j.ejca.2008.08.004
24. A.Cadoret, C.Ovejero, S.Saadi-Kheddouci, E.Souil, M.Fabre, B.Romagnolo, A.Kahn, C.Perret. Hepatomegaly in transgenic mice expressing an oncogenic form of beta-catenin. Cancer Res 2001; 61:3245-9; PMID:11309273
25. X.L.Bai, Q.Zhang, L.Y.Ye, F.Liang, X.Sun, Y.Chen, Q.D.Hu, Q.H.Fu, W.Su, Z.Chen, et al. Myocyte enhancer factor 2C regulation of hepatocellular carcinoma via vascular endothelial growth factor and Wnt/beta-catenin signaling. Oncogene 2015; 34:4089-97; PMID:25328135; http://dx.doi.org/10.1038/onc.2014.337
26. F.Pez, A.Lopez, M.Kim, J.R.Wands, C.Caron de Fromentel, P.Merle. Wnt signaling and hepatocarcinogenesis: molecular targets for the development of innovative anticancer drugs. J Hepatol 2013; 59:1107-17; PMID:23835194; http://dx.doi.org/10.1016/j.jhep.2013.07.001
27. L.Chen, M.Li, Q.Li, C.J.Wang, S.Q.Xie. DKK1 promotes hepatocellular carcinoma cell migration and invasion through beta-catenin/MMP7 signaling pathway. Mol Cancer 2013; 12:157; PMID:24325363; http://dx.doi.org/10.1186/1476-4598-12-157
28. P.Merle, S.de la Monte, M.Kim, M.Herrmann, S.Tanaka, A.Von Dem Bussche, M.C.Kew, C.Trepo, J.R.Wands. Functional consequences of frizzled-7 receptor overexpression in human hepatocellular carcinoma. Gastroenterology 2004; 127:1110-22; PMID:15480989; http://dx.doi.org/10.1053/j.gastro.2004.07.009
29. B.Chen, M.E.Dodge, W.Tang, J.Lu, Z.Ma, C.W.Fan, S.Wei, W.Hao, J.Kilgore, N.S.Williams, et al. Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. Nat Chem Biol 2009; 5:100-7; PMID:19125156; http://dx.doi.org/10.1038/nchembio.137
30. K.D.Proffitt, B.Madan, Z.Ke, V.Pendharkar, L.Ding, M.A.Lee, R.N.Hannoush, D.M.Virshup. Pharmacological inhibition of the Wnt acyltransferase PORCN prevents growth of WNT-driven mammary cancer. Cancer Res 2013; 73:502-7; PMID:23188502; http://dx.doi.org/10.1158/0008-5472.CAN-12-2258
31. J.Hu, A.Dong, V.Fernandez-Ruiz, J.Shan, M.Kawa, E.Martinez-Anso, J.Prieto, C.Qian. Blockade of Wnt signaling inhibits angiogenesis and tumor growth in hepatocellular carcinoma. Cancer Res 2009; 69:6951-9; PMID:19690140; http://dx.doi.org/10.1158/0008-5472.CAN-09-0541
32. H.Suzuki, D.N.Watkins, K.W.Jair, K.E.Schuebel, S.D.Markowitz, W.D.Chen, T.P.Pretlow, B.Yang, Y.Akiyama, M.Van Engeland, et al. Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Nat Gen 2004; 36:417-22; PMID:15034581; http://dx.doi.org/10.1038/ng1330
33. W.Lu, C.Lin, T.D.King, H.Chen, R.C.Reynolds, Y.Li. Silibinin inhibits Wnt/beta-catenin signaling by suppressing Wnt co-receptor LRP6 expression in human prostate and breast cancer cells. Cell Signal 2012; 24:2291-6; PMID:22820499; http://dx.doi.org/10.1016/j.cellsig.2012.07.009
34. W.Lu, C.Lin, M.J.Roberts, W.R.Waud, G.A.Piazza, Y.Li. Niclosamide suppresses cancer cell growth by inducing Wnt co-receptor LRP6 degradation and inhibiting the Wnt/beta-catenin pathway. PloS One 2011; 6:e29290; PMID:22195040; http://dx.doi.org/10.1371/journal.pone.0029290