Overactivation of the TGF-β pathway confers a mesenchymal-like phenotype and CXCR4-dependent migratory properties to liver tumor cells

Hepatology

Volumn 58, Issue 6, 2013, Pages 2032-2044

  Bertran, Esther ^a   Crosas Molist, Eva ^a   Sancho, Patricia ^a   Caja, Laia ^a   Lopez Luque, Judit ^a   Navarro, Estanislao ^a   Egea, Gustavo ^b   Lastra, Raquel ^c   Serrano, Teresa ^c   Ramos, Emilio ^c   Fabregat, Isabel ^a,b  

^a BELLVITGE BIOMEDICAL RESEARCH INSTITUTE IDIBELL   (Spain)

^b UNIVERSITY OF BARCELONA   (Spain)

^c HOSPITAL UNIVERSITARI DE BELLVITGE   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

CHEMOKINE RECEPTOR CXCR4; DIETHYLNITROSAMINE; TRANSFORMING GROWTH FACTOR BETA; PROTEIN SERINE THREONINE KINASE; STROMAL CELL DERIVED FACTOR 1; TGF-BETA TYPE I RECEPTOR; TRANSFORMING GROWTH FACTOR BETA RECEPTOR; TRANSFORMING GROWTH FACTOR BETA1;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; AUTOCRINE EFFECT; CANCER CELL CULTURE; CELL MIGRATION; CONTROLLED STUDY; GENE EXPRESSION; HUMAN; HUMAN CELL; HUMAN CELL CULTURE; HUMAN TISSUE; IMMUNOFLUORESCENCE; IMMUNOHISTOCHEMISTRY; LIVER CARCINOGENESIS; LIVER CELL CARCINOMA; MALE; MESENCHYME CELL; MOUSE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; RNA INTERFERENCE; WESTERN BLOTTING; AGED; ANIMAL; BIOSYNTHESIS; CELL MOTION; CHEMICALLY INDUCED; DRUG EFFECTS; EPITHELIAL MESENCHYMAL TRANSITION; EXPERIMENTAL LIVER NEOPLASM; FEMALE; LIVER TUMOR; METABOLISM; MIDDLE AGED; PATHOLOGY; PATHOPHYSIOLOGY; TUMOR CELL LINE; VERY ELDERLY;

AGED; AGED, 80 AND OVER; ANIMALS; CARCINOMA, HEPATOCELLULAR; CELL LINE, TUMOR; CELL MOVEMENT; CHEMOKINE CXCL12; DIETHYLNITROSAMINE; EPITHELIAL-MESENCHYMAL TRANSITION; FEMALE; HUMANS; LIVER NEOPLASMS; LIVER NEOPLASMS, EXPERIMENTAL; MALE; MICE; MIDDLE AGED; PROTEIN-SERINE-THREONINE KINASES; RECEPTORS, CXCR4; RECEPTORS, TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA1;

EID: 84888286377     PISSN: 02709139     EISSN: 15273350     Source Type: Journal    
DOI: 10.1002/hep.26597     Document Type: Article

References (34)

1. Massague J. TGFbeta in cancer. Cell 2008;134:215-230.
2. Valdes F, Murillo MM, Valverde AM, Herrera B, Sanchez A, Benito M, et al. Transforming growth factor-beta activates both pro-apoptotic and survival signals in fetal rat hepatocytes. Exp Cell Res 2004;292:209-218.
3. Caja L, Ortiz C, Bertran E, Murillo MM, Miro-Obradors MJ, Palacios E, et al. Differential intracellular signalling induced by TGF-beta in rat adult hepatocytes and hepatoma cells: implications in liver carcinogenesis. Cell Signal 2007;19:683-694.
4. Murillo MM, del Castillo G, Sanchez A, Fernandez M, Fabregat I. Involvement of EGF receptor and c-Src in the survival signals induced by TGF-beta1 in hepatocytes. Oncogene 2005;24:4580-4587.
5. Gotzmann J, Huber H, Thallinger C, Wolschek M, Jansen B, Schulte-Hermann R, et al. Hepatocytes convert to a fibroblastoid phenotype through the cooperation of TGF-beta1 and Ha-Ras: steps towards invasiveness. J Cell Sci 2002;115:1189-1202.
6. Valdes F, Alvarez AM, Locascio A, Vega S, Herrera B, Fernandez M, et al. The epithelial mesenchymal transition confers resistance to the apoptotic effects of transforming growth factor beta in fetal rat hepatocytes. Mol Cancer Res 2002;1:68-78.
7. Reichl P, Haider C, Grubinger M, Mikulits W. TGF-beta in epithelial to mesenchymal transition and metastasis of hepatocellular carcinoma. Curr Pharm Des 2012;18:4135-4147.
8. Giannelli G, Mazzocca A, Fransvea E, Lahn M, Antonaci S. Inhibiting TGF-beta signaling in hepatocellular carcinoma. Biochim Biophys Acta 2011;1815:214-223.
9. Coulouarn C, Factor VM, Thorgeirsson SS. Transforming growth factor-beta gene expression signature in mouse hepatocytes predicts clinical outcome in human cancer. Hepatology 2008;47:2059-2067.
10. Fransvea E, Angelotti U, Antonaci S, Giannelli G. Blocking transforming growth factor-beta up-regulates E-cadherin and reduces migration and invasion of hepatocellular carcinoma cells. Hepatology 2008;47:1557-1566.
11. Sheu BC, Chang WC, Cheng CY, Lin HH, Chang DY, Huang SC. Cytokine regulation networks in the cancer microenvironment. Front Biosci 2008;13:6255-6268.
12. Zlotnik A. New insights on the role of CXCR4 in cancer metastasis. J Pathol 2008;215:211-213.
13. Li W, Gomez E, Zhang Z. Immunohistochemical expression of stromal cell-derived factor-1 (SDF-1) and CXCR4 ligand receptor system in hepatocellular carcinoma. J Exp Clin Cancer Res 2007;26:527-533.
14. Sutton A, Friand V, Brule-Donneger S, Chaigneau T, Ziol M, Sainte-Catherine O, et al. Stromal cell-derived factor-1/chemokine (C-X-C motif) ligand 12 stimulates human hepatoma cell growth, migration, and invasion. Mol Cancer Res 2007;5:21-33.
15. Schimanski CC, Bahre R, Gockel I, Muller A, Frerichs K, Horner V, et al. Dissemination of hepatocellular carcinoma is mediated via chemokine receptor CXCR4. Br J Cancer 2006;95:210-217.
16. Bertran E, Caja L, Navarro E, Sancho P, Mainez J, Murillo MM, et al. Role of CXCR4/SDF-1alpha in the migratory phenotype of hepatoma cells that have undergone epithelial-mesenchymal transition in response to the transforming growth factor-beta. Cell Signal 2009;21:1595-1606.
17. Gonzalez-Rodriguez A, Clampit JE, Escribano O, Benito M, Rondinone CM, Valverde AM. Developmental switch from prolonged insulin action to increased insulin sensitivity in protein tyrosine phosphatase 1B-deficient hepatocytes. Endocrinology 2007;148:594-608.
18. Caja L, Sancho P, Bertran E, Ortiz C, Campbell JS, Fausto N, et al. The tyrphostin AG1478 inhibits proliferation and induces death of liver tumor cells through EGF receptor-dependent and independent mechanisms. Biochem Pharmacol 2011;82:1583-1592.
19. Caja L, Sancho P, Bertran E, Iglesias-Serret D, Gil J, Fabregat I. Overactivation of the MEK/ERK pathway in liver tumor cells confers resistance to TGF-{beta}-induced cell death through impairing up-regulation of the NADPH oxidase NOX4. Cancer Res 2009;69:7595-7602.
20. Morris SM, Baek JY, Koszarek A, Kanngurn S, Knoblaugh SE, Grady WM. Transforming growth factor-beta signaling promotes hepatocarcinogenesis induced by p53 loss. Hepatology 2012;55:121-131.
21. Baek HJ, Lim SC, Kitisin K, Jogunoori W, Tang Y, Marshall MB, et al. Hepatocellular cancer arises from loss of transforming growth factor beta signaling adaptor protein embryonic liver fodrin through abnormal angiogenesis. Hepatology 2008;48:1128-1137.
22. Matsuzaki K, Date M, Furukawa F, Tahashi Y, Matsushita M, Sugano Y, et al. Regulatory mechanisms for transforming growth factor beta as an autocrine inhibitor in human hepatocellular carcinoma: implications for roles of SMADs in its growth. Hepatology 2000;32:218-227.
23. Dooley S, Weng H, Mertens PR. Hypotheses on the role of transforming growth factor-beta in the onset and progression of hepatocellular carcinoma. Dig Dis 2009;27:93-101.
24. Murata M, Matsuzaki K, Yoshida K, Sekimoto G, Tahashi Y, Mori S, et al. Hepatitis B virus X protein shifts human hepatic transforming growth factor (TGF)-beta signaling from tumor suppression to oncogenesis in early chronic hepatitis B. Hepatology 2009;49:1203-1217.
25. Moustakas A, Heldin CH. Induction of epithelial-mesenchymal transition by transforming growth factor beta. Semin Cancer Biol 2012;22:446-454.
26. Fransvea E, Mazzocca A, Antonaci S, Giannelli G. Targeting transforming growth factor (TGF)-betaRI inhibits activation of beta1 integrin and blocks vascular invasion in hepatocellular carcinoma. Hepatology 2009;49:839-850.
27. Dooley S, ten Dijke P. TGF-beta in progression of liver disease. Cell Tissue Res 2012;347:245-256.
28. Franco DL, Mainez J, Vega S, Sancho P, Murillo MM, de Frutos CA, et al. Snail1 suppresses TGF-beta-induced apoptosis and is sufficient to trigger EMT in hepatocytes. J Cell Sci 2010;123:3467-3477.
29. Liu H, Pan Z, Li A, Fu S, Lei Y, Sun H, et al. Roles of chemokine receptor 4 (CXCR4) and chemokine ligand 12 (CXCL12) in metastasis of hepatocellular carcinoma cells. Cell Mol Immunol 2008;5:373-378.
30. Li N, Guo W, Shi J, Xue J, Hu H, Xie D, et al. Expression of the chemokine receptor CXCR4 in human hepatocellular carcinoma and its role in portal vein tumor thrombus. J Exp Clin Cancer Res 2010;29:156.
31. Zhang XH, Wang Q, Gerald W, Hudis CA, Norton L, Smid M, et al. Latent bone metastasis in breast cancer tied to Src-dependent survival signals. Cancer Cell 2009;16:67-78.
32. Katoh M, Katoh M. Integrative genomic analyses of CXCR4: transcriptional regulation of CXCR4 based on TGFbeta, Nodal, Activin signaling and POU5F1, FOXA2, FOXC2, FOXH1, SOX17, and GFI1 transcription factors. Int J Oncol 2010;36:415-420.
33. Seoane J. The TGFBeta pathway as a therapeutic target in cancer. Clin Transl Oncol 2008;10:14-19.
34. Duda DG, Kozin SV, Kirkpatrick ND, Xu L, Fukumura D, Jain RK. CXCL12 (SDF1alpha)-CXCR4/CXCR7 pathway inhibition: an emerging sensitizer for anticancer therapies? Clin Cancer Res 2011;17:2074-2080.