Cysteine cathepsins (Cts) also known as thiol proteinases belong to the superfamily of cysteine proteinases (EC 3.4.22). Cts are known as lysosomal proteases responsible for the intracellular proteins degradation. All Cts are synthesized as zymogens, activation of which occurs autocatalytically. Their activity is regulated by endogenous inhibitors. Cts can be secreted into the extracellular environment, which is of particular importance in tumor progression. Extracellular Cts not only hydrolyze extracellular matrix (ECM) proteins, but also contribute to ECM remodeling, processing and/or release of cell adhesion molecules, growth factors, cytokines and chemokines. In cancer, the expression and activity of Cts sharply increase both in cell lysosomes and in the intercellular space, which correlates with neoplastic transformation, invasion, metastasis and leads to further tumor progression. It has been shown that Cts expression depends on the cells type, therefore, their role in the tumor development differs depending on their cellular origin. The mechanism of Cts action in cancer is not limited only by their proteolytic action. The Cts influence on signal transduction pathways associated with cancer development, including the pathway involving growth factors, which is mediated through receptors tyrosine kinases (RTK) and various signaling mitogen-activated protein kinases (MAPK), has been proven. In addition, Cts are able to promote the epithelial-mesenchymal transition (EMT) by activating signal transduction pathways such as Wnt, Notch, and the pathway involving TGF-β. So, Ctc perform specific both destructive and regulatory functions, carrying out proteolysis, both inside and outside the cell.
Gureeva T.A., Timoshenko O.S., Kugaevskaya E.V., Solovyova N.I. (2021) Cysteine cathepsins: structure, physiological functions and their role in carcinogenesis. Biomeditsinskaya Khimiya, 67(6), 453-464.
Gureeva T.A. et al. Cysteine cathepsins: structure, physiological functions and their role in carcinogenesis // Biomeditsinskaya Khimiya. - 2021. - V. 67. -N 6. - P. 453-464.
Gureeva T.A. et al., "Cysteine cathepsins: structure, physiological functions and their role in carcinogenesis." Biomeditsinskaya Khimiya 67.6 (2021): 453-464.
Gureeva, T. A., Timoshenko, O. S., Kugaevskaya, E. V., Solovyova, N. I. (2021). Cysteine cathepsins: structure, physiological functions and their role in carcinogenesis. Biomeditsinskaya Khimiya, 67(6), 453-464.
Rudzińska M., Parodi A., Maslova V.D., Efremov Y.M., Gorokhovets N.V., Makarov V.A., Popkov V.A., Golovin A.V., Zernii E.Y., Zamyatnin A.A. (2020) Cancers, 12(2), 1310. CrossRef Scholar google search
Vizovišek M., Vidak E., Javoršek U., Mikhaylov G., Bratovš A., Turk B. (2020) Expert. Opin. Ther. Targets, 24(6), 573-588. CrossRef Scholar google search
Bromme D., Wilson S. (2011)in: Extracellular Matrix Degradation (Parks W.C., Mecham R.P., eds.), Springer: Berlin/Heidelberg, Germany, pp. 23-51. Scholar google search
Stoeckle C., Quecke P., Rückrich T., Burster T., Reich M., Weber E., Kalbacher H., Driessen C., Melms A., Tolosa E. (2012) J. Autoimmun., 38, 332-343. CrossRef Scholar google search
Tolosa E., Li W., Yasuda Y., Wienhold W., Denzin L.K., Lautwein A., Driessen C., Schnorrer P., Weber E., Stevanovic S., Kurek R., Melms A., Bromme D. (2003) J. Clin. Invest., 112, 517-526. CrossRef Scholar google search
Stoeckle C., Gouttefangeas C., Hammer M., Weber E., Melms A., Tolosa E. (2009) Exp. Hematol., 37, 266-275. CrossRef Scholar google search
Magister S., Obermajer N., Mirković B., Svajger U., Renko M., Softić A., Romih R., Colbert J.D., Watts C., Kos J. (2012) Eur. J. Cell. Biol., 91(5), 391-401. CrossRef Scholar google search
Sullivan S., Tosetto M., Kevans D., Coss A., Wang L., O'Donoghue D., Hyland J., Sheahan K., Mulcahy H., O'Sullivan J. (2009) Int. J. Cancer, 125(1), 54-61. CrossRef Scholar google search
Sloane B.F., Rozhin J., Johnson K., Taylor H., Crissman J.D., Honn K.V. (1986) Proc. Natl. Acad. Sci. USA, 83(8), 2483-2487. CrossRef Scholar google search
Droga-Mazovec G., Bojic L., Petelin A., Ivanova S., Romih R., Repnik U., Salvesen G.S., Stoka V., Turk V., Turk B. (2008) J. Biol. Chem., 283(27), 19140-19150. CrossRef Scholar google search
Quraishi O., Nägler D.K., Fox T., Sivaraman J., Cygler M., Mort J.S., Storer A.C. (1999) Biochemistry, 38(16), 5017-5023. CrossRef Scholar google search
Li Z., Yasuda Y., Li W., Bogyo M., Katz N., Gordon R.E., Fields G.B., Bromme D.J. (2004) J. Biol. Chem., 279(7), 5470-5479. CrossRef Scholar google search
Levičar N., Kos J., Blejec A., Golouh R., Vrhovec I., Frković-Grazio S., Lah T. (2002) Cancer Detect. Prev., 26(1), 42-49. CrossRef Scholar google search
Butler M.W., Fukui T., Salit J., Shaykhiev R., Mezey J.C., Hackett N.R., Crystal R.G. (2011) Cancer Res., 71, 2572-2581. CrossRef Scholar google search
Werle B., Schanzenbächer U., Lah T.T., Ebert E., Jülke B., Ebert W., Fiehn W., Kayser K., Spiess E., Abrahamson M., Kos J. (2006) Oncol. Rep., 16, 647-655. Scholar google search
Kos J., Krašovec M., Cimerman N., Nielsen H.J., Christensen I.J., Brünner N. (2000) Cancer Res., 6, 505-511. Scholar google search
Leto G., Tumminello F.M., Pizzolanti G., Montalto G., Soresi M., Gebbia N. (1997) Oncology, 54, 79-83. CrossRef Scholar google search
Mikhaylov G., Klimpel D., Schaschke N., Mikac U., Vizovišek M., Fonović M., Turk V., Turk B., Vasiljeva O. (2014) Angew. Chem. Int. Ed. Engl., 53(38), 10077-10081. CrossRef Scholar google search
Gocheva V., Zeng W., Ke D., Klimstra D., Reinheckel T., Peters C., Hanahan D., Joyce J. A. (2006) Genes Dev., 20, 543-556. CrossRef Scholar google search
Jevnikar Z., Rojnik M., Jamnik P., Doljak B., Fonović U.P., Kos J. (2013) J. Biol. Chem., 288, 2201-2209. CrossRef Scholar google search
Bossard M.J., Tomaszek T.A., Thompson S.K., Amegadzie B.Y., Hanning C.R., Jones C., Kurdyla J.T., McNulty D.E., Drake F.H., Gowen M. (1996) J. Biol. Chem., 271, 12517-12524. CrossRef Scholar google search
Small D.M., Burden R.E., Jaworski J., Hegarty S.M., Spence S., Burrows J.F., McFarlane C., Kissenpfennig A., McCarthy H.O., Johnston J.A., Walker B., Scott C.J. (2013) Int. J. Cancer, 133(9), 2102-2112. CrossRef Scholar google search
Fonović U.P., Jevnikar Z., Rojnik M., Doljak B., Fonović M., Jamnik P., Kos J. (2013) PLoS One, 8, e53918. CrossRef Scholar google search
Veillard F., Saidi A., Burden R.E., Scott C.J., Gillet L., Lecaille F., Lalmanach G. (2011) J. Biol. Chem., 286(43), 37158-37167. CrossRef Scholar google search
van Hinsbergh V.W., Engelse M.A., Quax P.H. (2006) Arterioscler. Thromb. Vasc. Biol., 26(4), 716-728. CrossRef Scholar google search
Chang S.H., Kanasaki K., Gocheva V., Blum G., Harper J., Moses M.A., Shih S.C., Nagy J.A., Joyce J., Bogyo M., Kalluri R., Dvorak H.F.( 2009) Cancer Res., 69(10), 4537-4544. CrossRef Scholar google search
Hallmann R., Horn N., Selg M., Wendler O., Pausch F., Sorokin L.M. (2005) Physiol. Rev., 85, 979-1000. CrossRef Scholar google search
Sloane B.F., Yan S., Podgorski I., Linebaugh B.E., Cher M.L., Mai J., Cavallo-Medved D., Sameni M., Dosescu J., Moin K. (2005) Semin. Cancer Biol., 15, 149-157. CrossRef Scholar google search
Wang B., Sun J., Kitamoto S., Yang M., Grubb A., Chapman H.A., Kalluri R., Shi G.-P. (2006) J. Biol. Chem., 281, 6020-6029. CrossRef Scholar google search
Navab R., Chevet E., Authier F., di Guglielmo G.M., Bergeron J.J., Brodt P. (2001) J. Biol. Chem., 276(17), 13644-13649. CrossRef Scholar google search
Teller A., Gopinath S., Alapati K., Gondi C.S., Gujrati M., Dinh D.H., Mohanam S., Rao J.S. (2015) Pathol. Res. Pract., 211(1), 62-70. Scholar google search
Chen K.L., Chang W.S., Cheung C.H., Lin C.C., Huang C.C., Yang Y.N., Kuo C.P., Kuo C.C., Chang Y.H., Liu K.J., Wu C.M., Chang J.Y. (2012) Cancer Lett., 317(1), 89-98. CrossRef Scholar google search
