Abstract
SAP-1 (stomach cancer-associated protein tyrosine phosphatase-1) is a transmembrane-type protein tyrosine phosphatase that has been implicated as a negative regulator of integrin-mediated signaling. The potential role of this enzyme in hepatocarcinogenesis has now been investigated by examining its expression in 32 surgically excised human hepatocellular carcinoma (HCC) specimens. Both immunohistochemical and immunoblot analyses revealed that normal liver tissue, as well as tissue affected by chronic hepatitis or cirrhosis, contained substantial amounts of SAP-1. The expression level of SAP-1 in 75% of well-differentiated HCCs was similar to or higher than that observed in the surrounding noncancerous tissue. In contrast, the abundance of SAP-1 in 85.7% of moderately differentiated HCCs and in all poorly differentiated HCCs was greatly reduced compared with that in the adjacent tissue. Indeed, SAP-1 was almost undetectable in 83.3% of poorly differentiated HCCs. Furthermore, expression of recombinant SAP-1 in two highly motile human HCC cell lines resulted in a change in morphology and a marked reduction in both migratory activity and growth rate. In conclusion, these results indicate that SAP-1 expression is downregulated during the dedifferentiation of human HCC, and that this downregulation may play a causal role in disease progression.
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References
Ardini E, Agresti R, Tagliabue E, Greco M, Aiello P, Yang LT, Menard S and Sap J . (2000). Oncogene, 19, 4979–4987.
Cantley LC, Auger KR, Carpenter C, Duckworth B, Graziani A, Kapeller R and Soltoff S . (1991). Cell, 64, 281–302.
De Vries L, Li RY, Ragab A, Ragab-Thomas JM and Chap H . (1991). FEBS Lett., 282, 285–288.
Doi I, Namba M and Sato J . (1975). Gann, 66, 385–392.
Edmondson HA and Steiner PE . (1954). Cancer, 7, 462–503.
Fantl WJ, Johnson DE and Williams LT . (1993). Annu. Rev. Biochem., 62, 453–481.
Genda T, Sakamoto M, Ichida T, Asakura H and Hirohashi S . (2000). Lab. Invest., 80, 387–394.
Genda T, Sakamoto M, Ichida T, Asakura H, Kojiro M, Narumiya S and Hirohashi S . (1999). Hepatology, 30, 1027–1036.
Hanks SK and Polte TR . (1997). BioEssays, 19, 137–145.
Higashitsuji H, Arii S, Furutani M, Imamura M, Kaneko Y, Takenawa J, Nakayama H and Fujita J . (1995). Oncogene, 10, 407–414.
Hunter T . (1995). Cell, 80, 225–236.
Ikuta S, Itoh F, Hinoda Y, Toyota M, Makiguchi Y and Imai K . (1994). J. Gastroenterol., 29, 727–732.
Imamura F, Mukai M, Ayaki M and Akedo H . (2000). Jpn. J. Cancer Res., 91, 811–816.
Ito Y, Sasaki Y, Horimoto M, Wada S, Tanaka Y, Kasahara A, Ueki T, Hirano T, Yamamoto H, Fujimoto J, Okamoto E, Hayashi N and Hori M . (1998). Hepatology, 27, 951–958.
Kameda T, Yasui W, Yoshida K, Tsujino T, Nakayama H, Ito M, Ito H and Tahara E . (1990). Cancer Res., 50, 8002–8009.
Kawate S, Fukusato T, Ohwada S, Watanuki A and Morishita Y . (1999). Oncology, 57, 157–163.
Keane MM, Lowrey GA, Ettenberg SA, Dayton MA and Lipkowitz S . (1996). Cancer Res., 56, 4236–4243.
Kim SR, Kang KB, Soh CG, Kim JH, Hayashi Y, Hanioka K and Itoh H . (1995). J. Gastroenterol. Hepatol., 10, 498–508.
Kitamura T, Nakamura K, Mizuno Y and Kikuchi K . (1995). Jpn. J. Cancer Res., 86, 811–818.
Klemke RL, Leng J, Molander R, Brooks PC, Vuori K and Cheresh DA . (1998). J. Cell Biol., 140, 961–972.
Krueger NX, Streuli M and Saito H . (1990). EMBO J., 9, 3241–3252.
LaForgia S, Morse B, Levy J, Barnea G, Cannizzaro LA, Li F, Nowell PC, Boghosian-Sell L, Glick J, Weston A, Harris CC, Drabkin H, Patterson D, Croce CM, Schlessinger J and Huebner K . (1991). Proc. Natl. Acad. Sci. USA, 88, 5036–5040.
Matozaki T, Suzuki T, Uchida T, Inazawa J, Ariyama T, Matsuda K, Horita K, Noguchi H, Mizuno H, Sakamoto C and Kasuga M . (1994). J. Biol. Chem., 269, 2075–2081.
Morita Y, Hayashi Y, Wang Y, Kanamaru T, Suzuki S, Ohta K, Yamamoto M, Saitoh Y, Itoh H and Doe WF . (1997). Hepatology, 25, 856–861.
Nishida N, Fukuda Y, Kokuryu H, Toguchida J, Yandell DW, Ikenaga M, Imura H and Ishizaki K . (1993). Cancer Res., 53, 368–372.
Noguchi T, Tsuda M, Takeda H, Takada T, Inagaki K, Yamao T, Fukunaga K, Matozaki T and Kasuga M . (2001). J. Biol. Chem., 276, 15216–15224.
Ojakian GK, Ratcliffe DR and Schwimmer R . (2001). J. Cell Sci., 114, 941–952.
Ostman A, Yang Q and Tonks NK . (1994). Proc. Natl. Acad. Sci. USA, 91, 9680–9684.
Palmer HJ, Tuzon CT and Paulson KE . (1999). J. Biol. Chem., 274, 11424–11430.
Rogler CE and Chisari FV . (1992). Semin. Liver Dis., 12, 265–278.
Saito S, Hashimoto N, Tokita K, Toyoda M, Suzuki Y, Goldstein BJ, Suzuki H, Makino H and Saito Y . (1996). Biochem. Biophys. Res. Commun., 227, 406–412.
Schlaepfer DD, Hauck CR and Sieg DJ . (1999). Prog. Biophys. Mol. Biol., 71, 435–478.
Seo Y, Matozaki T, Tsuda M, Hayashi Y, Itoh H and Kasuga M . (1997). Biochem. Biophys. Res. Commun., 231, 705–711.
Sugimura T . (1992). Science, 258, 603–607.
Tahara H, Nakanishi T, Kitamoto M, Nakashio R, Shay JW, Tahara E, Kajiyama G and Ide T . (1995). Cancer Res., 55, 2734–2736.
Takada T, Noguchi T, Inagaki K, Hosooka T, Fukunaga K, Yamao T, Ogawa W, Matozaki T and Kasuga M . (2002). J. Biol. Chem., 277, 34359–34366.
Tamura M, Gu J, Takino T and Yamada KM . (1999). Cancer Res., 59, 442–449.
Tian SS, Tsoulfas P and Zinn K . (1991). Cell, 67, 675–685.
Tonks NK . (1993). Semin. Cell Biol., 4, 373–377.
Tsukamoto T, Takahashi T, Ueda R, Hibi K and Saito H . (1992). Cancer Res., 52, 3506–3509.
Walton KM and Dixon JE . (1993). Annu. Rev. Biochem., 62, 101–120.
Acknowledgements
This study was supported by a grant-in-aid for scientific research (B)(2) 10470049 from the Ministry of Education, Science, Sports, and Culture of Japan.
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Nagano, H., Noguchi, T., Inagaki, K. et al. Downregulation of stomach cancer-associated protein tyrosine phosphatase-1 (SAP-1) in advanced human hepatocellular carcinoma. Oncogene 22, 4656–4663 (2003). https://doi.org/10.1038/sj.onc.1206588
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DOI: https://doi.org/10.1038/sj.onc.1206588
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