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Increased ERK phosphorylation and caveolin-1 expression on K562 human chronic myelogenous leukemia cells by jacalin, a dietary plant lectin

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Abstract

The potential antitumor effects of jacalin, the plant lectin that specifically recognizes the tumor-associated Thomsen-Friedenreich antigen has been extensively studied. We had earlier reported jacalin to be mitogenic to K562, the Bcr-Abl expressing erythroleukemia cell line. The dearth of studies highlighting the proliferative effects of jacalin and other lectins motivated us to unveil the mechanism underlying the mitogenic effects of jacalin. Caveolin-1 (cav-1) is an integral membrane protein, known to play a crucial role in cell signaling, lipid transport, and membrane trafficking. The role of cav-1 in tumorigenesis is considered to be controversial as it can suppress as well as promote tumor growth, depending on the cellular context. In the present study, we propose that cav-1 plays the central role in the mitogenic effects of jacalin on the K562 cells. In accordance, the mRNA, as well as protein expression of cav-1 was found to be upregulated in the jacalin-treated K562 cells as compared to the untreated control. Further, jacalin stimulation also increased the phosphorylation of ERK and Akt. The rationale that leads to the initial conjecture about cav-1 was that the sequence of jacalin possesses a cav-1-binding site.

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Abbreviations

cav-1:

Caveolin-1

References

  1. Sastry, M.V., Banarjee, P., Patanjali, S.R., Swamy, M.J., Swarnalatha, G.V., Surolia, A.: Analysis of saccharide binding to Artocarpus integrifolia lectin reveals specific recognition of T-antigen (beta-D-gal(1----3)D-GalNAc). J. Biol. Chem. 261(25), 11726–11733 (1986)

    Article  CAS  Google Scholar 

  2. Kabir, S.: Jacalin: a jackfruit (Artocarpus heterophyllus) seed-derived lectin of versatile applications in immunobiological research. J. Immunol. Methods. 212(2), 193–211 (1998)

    Article  CAS  Google Scholar 

  3. Lafont, V., Dornand, J., Covassin, L., Liautard, J.P., Favero, J.: The lectin jacalin triggers CD4-mediated lymphocyte signaling by binding CD4 through a protein-protein interaction. J. Leukoc. Biol. 59(5), 691–696 (1996)

    Article  CAS  Google Scholar 

  4. Komath, S.S., Bhanu, K., Maiya, B.G., Swamy, M.J.: Binding of porphyrins by the tumor-specific lectin, Jacalin [Jack fruit (Artocarpus integrifolia) agglutinin]. Biosci. Rep. 20(4), 265–276 (2000). https://doi.org/10.1023/a:1026440907227

    Article  CAS  PubMed  Google Scholar 

  5. Goel, M., Anuradha, P., Kaur, K.J., Maiya, B.G., Swamy, M.J., Salunke, D.M.: Porphyrin binding to jacalin is facilitated by the inherent plasticity of the carbohydrate-binding site: novel mode of lectin–ligand interaction. Acta Crystallogr. Sect. D. 60(2), 281–288 (2004). https://doi.org/10.1107/S0907444903026684

    Article  CAS  Google Scholar 

  6. Sahasrabuddhe, A.A., Ahmed, N., Krishnasastry, M.V.: Stress-induced phosphorylation of caveolin-1 and p38, and down-regulation of EGFr and ERK by the dietary lectin jacalin in two human carcinoma cell lines. Cell Stress Chaperones. 11(2), 135–147 (2006)

    Article  CAS  Google Scholar 

  7. Geraldino, T.H., Modiano, P., Veronez, L.C., Flória-Santos, M., Garcia, S.B., Pereira-da-Silva, G.: Jacalin has Chemopreventive effects on colon cancer development. Biomed. Res. Int. 4614357(10), 6 (2017)

    Google Scholar 

  8. Lavanya, V., Ahmed, N., Khan, M.K., Jamal, S.: Sustained mitogenic effect on K562 human chronic myelogenous leukemia cells by dietary lectin, jacalin. Glycoconj. J. 33(6), 877–886 (2016)

    Article  CAS  Google Scholar 

  9. Yang, H., Guan, L., Li, S., Jiang, Y., Xiong, N., Li, L., Wu, C., Zeng, H., Liu, Y.: Mechanosensitive caveolin-1 activation-induced PI3K/Akt/mTOR signaling pathway promotes breast cancer motility, invadopodia formation and metastasis in vivo. Oncotarget. 7(13), 16227 (2016)

    Article  Google Scholar 

  10. Meshulam, T., Simard, J.R., Wharton, J., Hamilton, J.A., Pilch, P.F.: Role of Caveolin-1 and cholesterol in transmembrane fatty acid movement. Biochemistry. 45(9), 2882–2893 (2006). https://doi.org/10.1021/bi051999b

    Article  CAS  PubMed  Google Scholar 

  11. Syme, C.A., Zhang, L., Bisello, A.: Caveolin-1 regulates cellular trafficking and function of the glucagon-like peptide 1 receptor. Mol. Endocrinol. 20(12), 3400–3411 (2006). https://doi.org/10.1210/me.2006-0178

    Article  CAS  PubMed  Google Scholar 

  12. Williams, T.M., Lisanti, M.P.: The caveolin proteins. Genome Biol. 5(3), 214–214 (2004). https://doi.org/10.1186/gb-2004-5-3-214

    Article  PubMed  PubMed Central  Google Scholar 

  13. Parolini, I., Sargiacomo, M., Galbiati, F., Rizzo, G., Grignani, F., Engelman, J.A., Okamoto, T., Ikezu, T., Scherer, P.E., Mora, R., Rodriguez-Boulan, E., Peschle, C., Lisanti, M.P.: Expression of caveolin-1 is required for the transport of caveolin-2 to the plasma membrane. Retention of caveolin-2 at the level of the golgi complex. J. Biol. Chem. 274(36), 25718–25725 (1999)

    Article  CAS  Google Scholar 

  14. Song, K.S., Scherer, P.E., Tang, Z., Okamoto, T., Li, S., Chafel, M., Chu, C., Kohtz, D.S., Lisanti, M.P.: Expression of Caveolin-3 in skeletal, cardiac, and smooth muscle cells: CAVEOLIN-3 IS a COMPONENT OF THE SARCOLEMMA AND CO-FRACTIONATES WITH DYSTROPHIN AND DYSTROPHIN-ASSOCIATED GLYCOPROTEINS*. J. Biol. Chem. 271(25), 15160–15165 (1996). https://doi.org/10.1074/jbc.271.25.15160

    Article  CAS  PubMed  Google Scholar 

  15. Fra, A.M., Williamson, E., Simons, K., Parton, R.G.: De novo formation of caveolae in lymphocytes by expression of VIP21-caveolin. Proc. Natl. Acad. Sci. U. S. A. 92(19), 8655–8659 (1995)

    Article  CAS  Google Scholar 

  16. Parton, R.G., Hanzal-Bayer, M., Hancock, J.F.: Biogenesis of caveolae: a structural model for caveolin-induced domain formation. J. Cell Sci. 119(Pt 5), 787–796 (2006)

    Article  CAS  Google Scholar 

  17. Wiechen, K., Diatchenko, L., Agoulnik, A., Scharff, K.M., Schober, H., Arlt, K., Zhumabayeva, B., Siebert, P.D., Dietel, M., Schäfer, R., Sers, C.: Caveolin-1 is down-regulated in human ovarian carcinoma and acts as a candidate tumor suppressor gene. Am. J. Pathol. 159(5), 1635–1643 (2001). https://doi.org/10.1016/s0002-9440(10)63010-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Huertas-Martínez, J., Rello-Varona, S., Herrero-Martín, D., Barrau, I., García-Monclús, S., Sáinz-Jaspeado, M., Lagares-Tena, L., Núñez-Álvarez, Y., Mateo-Lozano, S., Mora, J., Roma, J., Toran, N., Moran, S., López-Alemany, R., Gallego, S., Esteller, M., Peinado, M.A., Del Muro, X.G., Tirado, O.M.: Caveolin-1 is down-regulated in alveolar rhabdomyosarcomas and negatively regulates tumor growth. Oncotarget. 5(20), 9744–9755 (2014). https://doi.org/10.18632/oncotarget.2403

    Article  PubMed  PubMed Central  Google Scholar 

  19. Tirado, O.M., MacCarthy, C.M., Fatima, N., Villar, J., Mateo-Lozano, S., Notario, V.: Caveolin-1 promotes resistance to chemotherapy-induced apoptosis in Ewing's sarcoma cells by modulating PKCalpha phosphorylation. Int. J. Cancer. 126(2), 426–436 (2010). https://doi.org/10.1002/ijc.24754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Yuan, G., Regel, I., Lian, F., Friedrich, T., Hitkova, I., Hofheinz, R.D., Ströbel, P., Langer, R., Keller, G., Röcken, C., Zimmermann, W., Schmid, R.M., Ebert, M.P.A., Burgermeister, E.: WNT6 is a novel target gene of caveolin-1 promoting chemoresistance to epirubicin in human gastric cancer cells. Oncogene. 32(3), 375–387 (2013). https://doi.org/10.1038/onc.2012.40

    Article  CAS  PubMed  Google Scholar 

  21. Wang, Z., Wang, N., Liu, P., Peng, F., Tang, H., Chen, Q., Xu, R., Dai, Y., Lin, Y., Xie, X., Peng, C., Situ, H.: Caveolin-1, a stress-related oncotarget, in drug resistance. Oncotarget. 6(35), 37135–37150 (2015)

    Article  Google Scholar 

  22. Ting Tse, E.Y., Fat Ko, F.C., Kwan Tung, E.K., Chan, L.K., Wah Lee, T.K., Wai Ngan, E.S., Man, K., Tsai Wong, A.S., Ng, I.O.-L., Ping Yam, J.W.: Caveolin-1 overexpression is associated with hepatocellular carcinoma tumourigenesis and metastasis. J. Pathol. 226(4), 645–653 (2012). https://doi.org/10.1002/path.3957

    Article  CAS  Google Scholar 

  23. Basu Roy, U.K., Henkhaus, R.S., Loupakis, F., Cremolini, C., Gerner, E.W., Ignatenko, N.A.: Caveolin-1 is a novel regulator of K-RAS-dependent migration in colon carcinogenesis. Int. J. Cancer. 133(1), 43–57 (2013). https://doi.org/10.1002/ijc.28001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Shimizu, K., Kirita, K., Aokage, K., Kojima, M., Hishida, T., Kuwata, T., Fujii, S., Ochiai, A., Funai, K., Yoshida, J., Tsuboi, M., Ishii, G.: Clinicopathological significance of caveolin-1 expression by cancer-associated fibroblasts in lung adenocarcinoma. J. Cancer Res. Clin. Oncol. 143(2), 321–328 (2017)

    Article  CAS  Google Scholar 

  25. Liu, W.R., Jin, L., Tian, M.X., Jiang, X.F., Yang, L.X., Ding, Z.B., Shen, Y.H., Peng, Y.F., Gao, D.M., Zhou, J., Qiu, S.J., Dai, Z., Fan, J., Shi, Y.H.: Caveolin-1 promotes tumor growth and metastasis via autophagy inhibition in hepatocellular carcinoma. Clin Res Hepatol Gastroenterol. 40(2), 169–178 (2016)

    Article  CAS  Google Scholar 

  26. Ruan, H., Li, X., Yang, H., Song, Z., Tong, J., Cao, Q., Wang, K., Xiao, W., Xiao, H., Chen, X., Xu, G., Bao, L., Xiong, Z., Yuan, C., Liu, L., Qu, Y., Hu, W., Gao, Y., Ru, Z., Chen, K., Zhang, X.: Enhanced expression of caveolin-1 possesses diagnostic and prognostic value and promotes cell migration, invasion and sunitinib resistance in the clear cell renal cell carcinoma. Exp. Cell Res. 358(2), 269–278 (2017)

    Article  CAS  Google Scholar 

  27. Glenney Jr., J.R., Soppet, D.: Sequence and expression of caveolin, a protein component of caveolae plasma membrane domains phosphorylated on tyrosine in Rous sarcoma virus-transformed fibroblasts. Proc. Natl. Acad. Sci. U. S. A. 89(21), 10517–10521 (1992)

    Article  CAS  Google Scholar 

  28. Boscher, C., Nabi, I.R.: Caveolin-1: role in cell signaling. Adv. Exp. Med. Biol. 729, 29–50 (2012)

    Article  CAS  Google Scholar 

  29. Fridolfsson, H.N., Roth, D.M., Insel, P.A., Patel, H.H.: Regulation of intracellular signaling and function by caveolin. FASEB J. 28(9), 3823–3831 (2014). https://doi.org/10.1096/fj.14-252320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Qin, L.J., Jia, Y.S., Zhang, Y.B., Wang, Y.H.: Interleukin-1β induces the upregulation of caveolin-1 expression in a rat brain tumor model. Biomed Rep. 4(4), 433–436 (2016)

    Article  CAS  Google Scholar 

  31. Bae, G.D., Park, E.-Y., Kim, K., Jang, S.-E., Jun, H.-S., Oh, Y.S.: Upregulation of caveolin-1 and its colocalization with cytokine receptors contributes to beta cell apoptosis. Sci. Rep. 9(1), 16785 (2019). https://doi.org/10.1038/s41598-019-53278-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Faheina-Martins, G.V., da Silveira, A.L., Ramos, M.V., Marques-Santos, L.F., Araujo, D.A.: Influence of fetal bovine serum on cytotoxic and genotoxic effects of lectins in MCF-7 cells. J. Biochem. Mol. Toxicol. 25(5), 290–296 (2011)

    Article  CAS  Google Scholar 

  33. Fra, A.M., Williamson, E., Simons, K., Parton, R.G.: Detergent-insoluble glycolipid microdomains in lymphocytes in the absence of caveolae. J. Biol. Chem. 269(49), 30745–30748 (1994)

    Article  CAS  Google Scholar 

  34. Sager, R., Sheng, S., Anisowicz, A., Sotiropoulou, G., Zou, Z., Stenman, G., Swisshelm, K., Chen, Z., Hendrix, M.J., Pemberton, P., et al.: RNA genetics of breast cancer: maspin as paradigm. Cold Spring Harb. Symp. Quant. Biol. 59, 537–546 (1994)

    Article  CAS  Google Scholar 

  35. Ma, W., Wang, D.D., Li, L., Feng, Y.K., Gu, H.M., Zhu, G.M., Piao, J.H., Yang, Y., Gao, X., Zhang, P.X.: Caveolin-1 plays a key role in the oleanolic acid-induced apoptosis of HL-60 cells. Oncol. Rep. 32(1), 293–301 (2014)

    Article  CAS  Google Scholar 

  36. Li, L., Ren, C.H., Tahir, S.A., Ren, C., Thompson, T.C.: Caveolin-1 maintains activated Akt in prostate cancer cells through scaffolding domain binding site interactions with and inhibition of serine/threonine protein phosphatases PP1 and PP2A. Mol. Cell. Biol. 23(24), 9389–9404 (2003)

    Article  CAS  Google Scholar 

  37. Hehlgans, S., Eke, I., Storch, K., Haase, M., Baretton, G.B., Cordes, N.: Caveolin-1 mediated radioresistance of 3D grown pancreatic cancer cells. Radiother. Oncol. 92(3), 362–370 (2009). https://doi.org/10.1016/j.radonc.2009.07.004

    Article  CAS  PubMed  Google Scholar 

  38. Henkhaus, R.S., Roy, U.K., Cavallo-Medved, D., Sloane, B.F., Gerner, E.W., Ignatenko, N.A.: Caveolin-1-mediated expression and secretion of kallikrein 6 in colon cancer cells. Neoplasia. 10(2), 140–148 (2008)

    Article  CAS  Google Scholar 

  39. Vetterkind, S., Poythress, R.H., Lin, Q.Q., Morgan, K.G.: Hierarchical scaffolding of an ERK1/2 activation pathway. Cell Commun Signal. 11(1), 65 (2013). https://doi.org/10.1186/1478-811x-11-65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Arpaia, E., Blaser, H., Quintela-Fandino, M., Duncan, G., Leong, H.S., Ablack, A., Nambiar, S.C., Lind, E.F., Silvester, J., Fleming, C.K., Rufini, A., Tusche, M.W., Brüstle, A., Ohashi, P.S., Lewis, J.D., Mak, T.W.: The interaction between caveolin-1 and rho-GTPases promotes metastasis by controlling the expression of alpha5-integrin and the activation of Src, Ras and Erk. Oncogene. 31(7), 884–896 (2012)

    Article  CAS  Google Scholar 

  41. Song, G., Ouyang, G., Bao, S.: The activation of Akt/PKB signaling pathway and cell survival. J. Cell. Mol. Med. 9(1), 59–71 (2005)

    Article  CAS  Google Scholar 

  42. Vincent, E.E., Elder, D.J., Thomas, E.C., Phillips, L., Morgan, C., Pawade, J., Sohail, M., May, M.T., Hetzel, M.R., Tavaré, J.M.: Akt phosphorylation on Thr308 but not on Ser473 correlates with Akt protein kinase activity in human non-small cell lung cancer. Br. J. Cancer. 104(11), 1755–1761 (2011)

    Article  CAS  Google Scholar 

  43. Seshacharyulu, P., Pandey, P., Datta, K., Batra, S.K.: Phosphatase: PP2A structural importance, regulation and its aberrant expression in cancer. Cancer Lett. 335(1), 9–18 (2013)

    Article  CAS  Google Scholar 

  44. Yamada, T., Katagiri, H., Asano, T., Inukai, K., Tsuru, M., Kodama, T., Kikuchi, M., Oka, Y.: 3-phosphoinositide-dependent protein kinase 1, an Akt1 kinase, is involved in dephosphorylation of Thr-308 of Akt1 in Chinese hamster ovary cells. J. Biol. Chem. 276(7), 5339–5345 (2001)

    Article  CAS  Google Scholar 

  45. Kuo, Y.C., Huang, K.Y., Yang, C.H., Yang, Y.S., Lee, W.Y., Chiang, C.W.: Regulation of phosphorylation of Thr-308 of Akt, cell proliferation, and survival by the B55alpha regulatory subunit targeting of the protein phosphatase 2A holoenzyme to Akt. J. Biol. Chem. 283(4), 1882–1892 (2008)

    Article  CAS  Google Scholar 

  46. Couet, J., Sargiacomo, M., Lisanti, M.P.: Interaction of a receptor tyrosine kinase, EGF-R, with caveolins. Caveolin binding negatively regulates tyrosine and serine/threonine kinase activities. J. Biol. Chem. 272(48), 30429–30438 (1997)

    Article  CAS  Google Scholar 

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  1. School of Life Sciences, B S A Crescent Institute of Science and Technology, Vandalur, Chennai, Tamil Nadu, 600048, India

    Lavanya V, Shazia Jamal & Neesar Ahmed

  2. Department of Biotechnology, Guru Nanak College, Velachery, Chennai, Tamil Nadu, 600042, India

    Lavanya V

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V, L., Jamal, S. & Ahmed, N. Increased ERK phosphorylation and caveolin-1 expression on K562 human chronic myelogenous leukemia cells by jacalin, a dietary plant lectin. Glycoconj J 38, 361–368 (2021). https://doi.org/10.1007/s10719-021-09998-4

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