[en] Galectin-3, a multifunctional lectin, is involved during cancer progression. Previous observations showed that both cytosolic expression and nuclear exclusion of galectin-3 in human prostate cancer cells were associated to progression of the disease. In this study, we examined the biological roles of galectin-3 when expressed either in the nucleus or in the cytosol. LNCaP, a galectin-3-negative human prostate cancer cell line, was used to generate transfectants expressing galectin-3 either in the nucleus or in the cytosol. No changes in cell morphology, proliferation, attachment to laminin-1 or androgen dependency were observed. Cytoplasmic galectin-3 induced significantly increased Matrigel invasion, anchorage-independent growth and in vivo tumor growth and angiogenesis, and decreased inducible apoptosis. Surprisingly, nuclear galectin-3 affected these parameters in an opposite fashion with an overall antitumoral activity. Thus, our study demonstrates that galectin-3 exerts opposite biological activities according to its cellular localization: nuclear galectin-3 plays antitumor functions and cytoplasmic galectin-3 promotes tumor progression.
Korkmaz, K.S., Korkmaz, C.G., Ragnhildstveit, E., Kizildag, S., Pretlow, T.G., Saatcioglu, F., (2000) Gene, 260, pp. 25-36
Kyprianou, N., King, E.D., Bradbury, D., Rhee, J.G., (1997) Int. J. Cancer, 70, pp. 341-348
Le Marer, N., Bruyneel, E., (1996) Anticancer Res., 16, pp. 2767-2772
Le Marer, N., Hughes, R.C., (1996) J. Cell. Physiol., 168, pp. 51-58
Lin, H.M., Pestell, R.G., Raz, A., Kim, H.R., (2002) Oncogene, 21, pp. 8001-8010
Locigno, R., Pincemail, J., Henno, A., Treusch, G., Castronovo, V., (2002) Int. J. Oncol., 20, pp. 69-75
Lotz, M.M., Andrews Jr., C.W., Korzelius, C.A., Lee, E.C., Steele Jr., G.D., Clarke, A., Mercurio, A.M., (1993) Proc. Natl. Acad. Sci. USA, 90, pp. 3466-3470
Matarrese, P., Fusco, O., Tinari, N., Natoli, C., Liu, F.T., Semeraro, M.L., Malorni, W., Iacobelli, S., (2000) Int. J. Cancer, 85, pp. 545-554
Matarrese, P., Tinari, N., Semeraroa, M.L., Natolib, C., Iacobelli, S., Malorni, W., (2000) FEBS Lett., 473, pp. 311-315
Moon, B.K., Lee, Y.J., Battle, P., Jessup, J.M., Raz, A., Kim, H.R., (2001) Am. J. Pathol., 159, pp. 1055-1060
Moutsatsos, I.K., Wade, M., Schindler, M., Wang, J.L., (1987) Proc. Natl. Acad. Sci. USA, 84, pp. 6452-6456
Muenchen, H.J., Lin, D.L., Walsh, M.A., Keller, E.T., Pienta, K.J., (2000) Clin. Cancer Res., 6, pp. 1969-1977
Nangia-Makker, P., Honjo, Y., Sarvis, R., Akahani, S., Hogan, V., Pienta, K.J., Raz, A., (2000) Am. J. Pathol., 156, pp. 899-909
Nangia-Makker, P., Thompson, E., Hogan, C., Ochieng, J., Raz, A., (1995) Int. J. Oncol., 7, pp. 1079-1087
Nesterov, A., Lu, X., Johnson, M., Miller, G.J., Ivashchenko, Y., Kraft, A.S., (2001) J. Biol. Chem., 276, pp. 10767-10774
Noel, A., Simon, N., Raus, J., Foidart, J.M., (1992) Biochem. Pharmacol., 43, pp. 1263-1267
Park, J.W., Voss, P.G., Grabski, S., Wang, J.L., Patterson, R.J., (2001) Nucleic. Acids Res., 29, pp. 3595-3602
Paron, I., Scaloni, A., Pines, A., Bachi, A., Liu, F.T., Puppin, C., Pandolfi, M., Tell, G., (2003) Biochem. Biophys. Res. Commun., 302, pp. 545-553
Raz, A., Zhu, D.G., Hogan, V., Shah, N., Raz, T., Karkash, R., Pazerini, G., Carmi, P., (1990) Int. J. Cancer, 46, pp. 871-877
Robertson, M.W., Albrandt, K., Keller, D., Liu, F.T., (1990) Biochemistry, 29, pp. 8093-8100
Rodriguez, J., Lazebnik, Y., (1999) Genes Dev., 13, pp. 3179-3184
Sanjuan, X., Fernandez, P.L., Castells, A., Castronovo, V., Van Den Brule, F., Liu, F.T., Cardesa, A., Campo, E., (1997) Gastroenterology, 113, pp. 1906-1915
Sato, S., Hughes, R.C., (1994) J. Biol. Chem., 269, pp. 4424-4430
Song, Y.K., Billiar, T.R., Lee, Y.J., (2002) Am. J. Pathol., 160, pp. 1069-1075
Stennicke, H.R., Deveraux, Q.L., Humke, E.W., Reed, J.C., Dixit, V.M., Salvesen, G.S., (1999) J. Biol. Chem., 274, pp. 8359-8362
Takenaka, Y., Fukumori, T., Yoshii, T., Oka, N., Inohara, H., Kim, H.R., Bresalier, R.S., Raz, A., (2004) Mol. Cell Biol., 24, pp. 4395-4406