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Clinical & Experimental Metastasis
Published in: Clinical & Experimental Metastasis 2/2010

01-02-2010 | Research Paper

FAK is involved in invasion and metastasis of hepatocellular carcinoma

Authors: Jing-Song Chen, Xiao-Hui Huang, Qian Wang, Xi-Lin Chen, Xin-Hui Fu, Hao-Xiang Tan, Long-Juan Zhang, Wen Li, Jiong Bi

Published in: Clinical & Experimental Metastasis | Issue 2/2010

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Abstract

Studies have shown that focal adhesion kinase (FAK) is overexpressed in several human tumors and plays an important role in tumor progression. However, the role and underlying mechanisms of FAK in hepatocellular carcinoma (HCC) progression remains to be elucidated. In this study, we examined FAK and phosphorylated FAK Tyr397 expression in a large series of HCCs. We found that both FAK and phosphorylated FAK Tyr397 were overexpressed in HCC samples and HCC cell lines. Increased FAK and phosphorylated FAK Tyr397 expressions were correlated with tumor stage, vascular invasion and intrahepatic metastasis in HCC. Furthermore, HCC cell adhesion, migration and invasion were substantially impaired by siRNA-mediated knockdown of FAK expression, whereas cell growth, apoptosis and cell cycle distribution were not affected. In addition, depletion of FAK induced a significant reduction in expressions and activities of both MMP-2 and MMP-9. Taken together, FAK contributes to invasion and metastasis of HCC partly through regulating expressions and activations of both MMP-2 and MMP-9, suggesting FAK could be a promising therapeutic target for HCC.
Literature
1.
2.
McLean GW, Carragher NO, Avizienyte E, Evans J, Brunton VG, Frame MC (2005) The role of focal-adhesion kinase in cancer—a new therapeutic opportunity. Nat Rev Cancer 5(7):505–515CrossRefPubMed
3.
Siesser PM, Hanks SK (2006) The signaling and biological implications of FAK overexpression in cancer. Clin Cancer Res 12(11 Pt 1):3233–3237CrossRefPubMed
4.
Schlaepfer DD, Mitra SK, Ilic D (2004) Control of motile and invasive cell phenotypes by focal adhesion kinase. Biochim Biophys Acta 1692(2–3):77–102PubMed
5.
Chen HC, Appeddu PA, Isoda H, Guan JL (1996) Phosphorylation of tyrosine 397 in focal adhesion kinase is required for binding phosphatidylinositol 3-kinase. J Biol Chem 271(42):26329–26334CrossRefPubMed
6.
Chen HC, Guan JL (1994) Association of focal adhesion kinase with its potential substrate phosphatidylinositol 3-kinase. Proc Natl Acad Sci USA 91(21):10148–10152CrossRefPubMed
7.
Igishi T, Fukuhara S, Patel V, Katz BZ, Yamada KM, Gutkind JS (1999) Divergent signaling pathways link focal adhesion kinase to mitogen-activated protein kinase cascades. Evidence for a role of paxillin in c-Jun NH(2)-terminal kinase activation. J Biol Chem 274(43):30738–30746CrossRefPubMed
8.
Almeida EA, Ilić D, Han Q, Hauck CR, Jin F, Kawakatsu H et al (2000) Matrix survival signaling: from fibronectin via focal adhesion kinase to c-Jun NH(2)-terminal kinase. J Cell Biol 149(3):741–754CrossRefPubMed
9.
Kim SJ, Park JW, Yoon JS, Mok JO, Kim YJ, Park HK et al (2004) Increased expression of focal adhesion kinase in thyroid cancer: immunohistochemical study. J Korean Med Sci 19(5):710–715CrossRefPubMed
10.
Lark AL, Livasy CA, Dressler L, Moore DT, Millikan RC, Geradts J et al (2005) High focal adhesion kinase expression in invasive breast carcinomas is associated with an aggressive phenotype. Mod Pathol 18(10):1289–1294CrossRefPubMed
11.
Miyazaki T, Kato H, Nakajima M, Sohda M, Fukai Y, Masuda N et al (2003) FAK overexpression is correlated with tumour invasiveness and lymph node metastasis in oesophageal squamous cell carcinoma. Br J Cancer 89(1):140–145CrossRefPubMed
12.
Lark AL, Livasy CA, Calvo B, Caskey L, Moore DT, Yang X et al (2003) Overexpression of focal adhesion kinase in primary colorectal carcinomas and colorectal liver metastases: immunohistochemistry and real-time PCR analyses. Clin Cancer Res 9(1):215–222PubMed
13.
Rovin JD, Frierson HF Jr, Ledinh W, Parsons JT, Adams RB (2002) Expression of focal adhesion kinase in normal and pathologic human prostate tissues. Prostate 53(2):124–132CrossRefPubMed
14.
Beierle EA, Massoll NA, Hartwich J, Kurenova EV, Golubovskaya VM, Cance WG et al (2008) Focal adhesion kinase expression in human neuroblastoma: immunohistochemical and real-time PCR analyses. Clin Cancer Res 14(11):3299–3305CrossRefPubMed
15.
Fujii T, Koshikawa K, Nomoto S, Okochi O, Kaneko T, Inoue S et al (2004) Focal adhesion kinase is overexpressed in hepatocellular carcinoma and can be served as an independent prognostic factor. J Hepatol 41(1):104–111CrossRefPubMed
16.
Itoh S, Maeda T, Shimada M, Aishima S, Shirabe K, Tanaka S et al (2004) Role of expression of focal adhesion kinase in progression of hepatocellular carcinoma. Clin Cancer Res 10(8):2812–2817CrossRefPubMed
17.
Chen JS, Wang Q, Fu XH, Huang XH, Chen XL, Cao LQ et al (2009) Involvement of PI3K/PTEN/AKT/mTOR pathway in invasion and metastasis in hepatocellular carcinoma: association with MMP-9. Hepatol Res 39(2):177–186CrossRefPubMed
18.
Giannelli G, Bergamini C, Marinosci F, Fransvea E, Quaranta M, Lupo L et al (2002) Clinical role of MMP-2/TIMP-2 imbalance in hepatocellular carcinoma. Int J Cancer 97(4):425–431CrossRefPubMed
19.
Giannelli G, Fransvea E, Bergamini C, Marinosci F, Antonaci S (2003) Laminin-5 chains are expressed differentially in metastatic and nonmetastatic hepatocellular carcinoma. Clin Cancer Res 9(10 Pt 1):3684–3691PubMed
20.
Fransvea E, Angelotti U, Antonaci S, Giannelli G (2008) Blocking transforming growth factor-beta up-regulates E-cadherin and reduces migration and invasion of hepatocellular carcinoma cells. Hepatology 47(5):1557–1566CrossRefPubMed
21.
Ren K, Jin H, Bian C, He H, Liu X, Zhang S et al (2008) MR-1 modulates proliferation and migration of human hepatoma HepG2 cells through myosin light chains-2 (MLC2)/focal adhesion kinase (FAK)/Akt signaling pathway. J Biol Chem 283(51):35598–35605CrossRefPubMed
22.
Hauck CR, Hsia DA, Puente XS, Cheresh DA, Schlaepfer DD (2002) FRNK blocks v-Src-stimulated invasion and experimental metastases without effects on cell motility or growth. EMBO J 21(23):6289–62302CrossRefPubMed
23.
Bawadi HA, Bansode RR, Trappey A 2nd, Truax RE, Losso JN (2005) Inhibition of Caco-2 colon, MCF-7 and Hs578T breast, and DU 145 prostatic cancer cell proliferation by water-soluble black bean condensed tannins. Cancer Lett 218(2):153–162CrossRefPubMed
24.
Schlaepfer DD, Hauck CR, Sieg DJ (1999) Signaling through focal adhesion kinase. Prog Biophys Mol Biol 71(3–4):435–478CrossRefPubMed
25.
Schaller MD (2001) Biochemical signals and biological responses elicited by the focal adhesion kinase. Biochim Biophys Acta 1540(1):1–21CrossRefPubMed
26.
Liotta LA (1986) Tumor invasion and metastases—role of the extracellular matrix: Rhoads Memorial Award lecture. Cancer Res 46(1):1–7PubMed
27.
Curran S, Murray GI (1999) Matrix metalloproteinases in tumour invasion and metastasis. J Pathol 189(3):300–308CrossRefPubMed
28.
Vihinen P, Kähäri VM (2002) Matrix metalloproteinases in cancer: prognostic markers and therapeutic targets. Int J Cancer 99(2):157–166CrossRefPubMed
29.
Vihinen P, Ala-aho R, Kähäri VM (2005) Matrix metalloproteinases as therapeutic targets in cancer. Curr Cancer Drug Targets 5(3):203–220CrossRefPubMed
30.
31.
Duxbury MS, Ito H, Benoit E, Zinner MJ, Ashley SW, Whang EE (2003) RNA interference targeting focal adhesion kinase enhances pancreatic adenocarcinoma gemcitabine chemosensitivity. Biochem Biophys Res Commun 311(3):786–792CrossRefPubMed
32.
Mitra SK, Lim ST, Chi A, Schlaepfer DD (2006) Intrinsic focal adhesion kinase activity controls orthotopic breast carcinoma metastasis via the regulation of urokinase plasminogen activator expression in a syngeneic tumor model. Oncogene 25(32):4429–4440CrossRefPubMed
33.
Canel M, Secades P, Garzón-Arango M, Allonca E, Suarez C, Serrels A et al (2008) Involvement of focal adhesion kinase in cellular invasion of head and neck squamous cell carcinomas via regulation of MMP-2 expression. Br J Cancer 98(7):1274–1284CrossRefPubMed
34.
Tsutsumi K, Kasaoka T, Park HM, Nishiyama H, Nakajima M, Honda T (2008) Tumor growth inhibition by synthetic and expressed siRNA targeting focal adhesion kinase. Int J Oncol 33(1):215–224PubMed
35.
Sonoda Y, Matsumoto Y, Funakoshi M, Yamamoto D, Hanks SK, Kasahara T (2000) Anti-apoptotic role of focal adhesion kinase (FAK). Induction of inhibitor-of-apoptosis proteins and apoptosis suppression by the overexpression of FAK in a human leukemic cell line, HL-60. J Biol Chem 275(21):16309–16315CrossRefPubMed
36.
Wu ZM, Yuan XH, Jiang PC, Li ZQ, Wu T (2006) Antisense oligonucleodes targeting the focal adhesion kinase inhibit proliferation, induce apoptosis and cooperate with cytotoxic drugs in human glioma cells. J Neurooncol 77(2):117–123CrossRefPubMed
37.
Jiang Y, Goldberg ID, Shi YE (2002) Complex roles of tissue inhibitors of metalloproteinases in cancer. Oncogene 21(14):2245–2252CrossRefPubMed
38.
Sein TT, Thant AA, Hiraiwa Y, Amin AR, Sohara Y, Liu Y et al (2000) A role for FAK in the Concanavalin A-dependent secretion of matrix metalloproteinase-2 and -9. Oncogene 19(48):5539–5542CrossRefPubMed
39.
Hauck CR, Sieg DJ, Hsia DA, Loftus JC, Gaarde WA, Monia BP et al (2001) Inhibition of focal adhesion kinase expression or activity disrupts epidermal growth factor-stimulated signaling promoting the migration of invasive human carcinoma cells. Cancer Res 61(19):7079–7090PubMed
40.
Mon NN, Ito S, Senga T, Hamaguchi M (2006) FAK signaling in neoplastic disorders: a linkage between inflammation and cancer. Ann N Y Acad Sci 1086:199–212CrossRefPubMed
41.
Halder J, Landen CN Jr, Lutgendorf SK, Li Y, Jennings NB, Fan D et al (2005) Focal adhesion kinase silencing augments docetaxel-mediated apoptosis in ovarian cancer cells. Clin Cancer Res 11:8829–8836CrossRefPubMed
Metadata
Title
FAK is involved in invasion and metastasis of hepatocellular carcinoma
Authors
Jing-Song Chen
Xiao-Hui Huang
Qian Wang
Xi-Lin Chen
Xin-Hui Fu
Hao-Xiang Tan
Long-Juan Zhang
Wen Li
Jiong Bi
Publication date
01-02-2010
Publisher
Springer Netherlands
Published in
Clinical & Experimental Metastasis / Issue 2/2010
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-010-9306-3

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