DOI QR코드

DOI QR Code

Clinical Significance of SH2B1 Adaptor Protein Expression in Non-small Cell Lung Cancer

  • Zhang, Hang (Department of Cardiothoracic Surgery Xiangya Hospital, Central South University) ;
  • Duan, Chao-Jun (Medical Science Institute, Xiangya Hospital, Central South University) ;
  • Chen, Wei (Department of Cardiothoracic Surgery Xiangya Hospital, Central South University) ;
  • Wang, Shao-Qiang (Department of Cardiothoracic Surgery Xiangya Hospital, Central South University) ;
  • Zhang, Sheng-Kang (Department of Cardiothoracic Surgery Xiangya Hospital, Central South University) ;
  • Dong, Shuo (Department of Cardiothoracic Surgery Xiangya Hospital, Central South University) ;
  • Cheng, Yuan-Da (Department of Cardiothoracic Surgery Xiangya Hospital, Central South University) ;
  • Zhang, Chun-Fang (Department of Cardiothoracic Surgery Xiangya Hospital, Central South University)
  • 발행 : 2012.05.30

초록

The SH2B1 adaptor protein is recruited to multiple ligand-activated receptor tyrosine kinases that play important role in the physiologic and pathologic features of many cancers. The purpose of this study was to assess SH2B1 expression and to explore its contribution to the non-small cell lung cancer (NSCLC). Methods: SH2B1 expression in 114 primary NSCLC tissue specimens was analyzed by immunohistochemistry and correlated with clinicopathological parameters and patients' outcome. Additionally, 15 paired NSCLC background tissues, 5 NSCLC cell lines and a normal HBE cell line were evaluated for SH2B1 expression by RT-PCR and immunoblotting, immunofluorescence being applied for the cell lines. Results: SH2B1 was found to be overexpressed in NSCLC tissues and NSCLC cell lines. More importantly, high SH2B1 expression was significantly associated with tumor grade, tumor size, clinical stage, lymph node metastasis, and recurrence respectively. Survival analysis demonstrated that patients with high SH2B1 expression had both poorer disease-free survival and overall survival than other patients. Multivariate Cox regression analysis revealed that SH2B1 overexpression was an independent prognostic factor for patients with NSCLC. Conclusions: Our findings suggest that the SH2B1 protein may contribute to the malignant progression of NSCLC and could offer a novel prognostic indicator for patients with NSCLC.

키워드

참고문헌

  1. Ahmad I, Singh LB, Foth M, et al (2011). K-Ras and $\beta$-catenin mutations cooperate with Fgfr3 mutations in mice to promote tumorigenesis in the skin and lung, but not in the bladder. Dis Model Mech, 4, 548-55. https://doi.org/10.1242/dmm.006874
  2. Bahrenberg G, Behrmann I, Barthel A, et al (2002). Identification of the critical sequence elements in the cytoplasmic domain of leptin receptor isoforms required for Janus kinase/signal transducer and a ctivator of transcription activation by receptor heterodimers. Mol Endocrinol, 16, 859-72. https://doi.org/10.1210/me.16.4.859
  3. Balch CM, Gershenwald JE, Soong SJ, et al (2009). Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol, 27, 6199-206. https://doi.org/10.1200/JCO.2009.23.4799
  4. Cappellen D, De Oliverira C, Ricol D, et al (1999). Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas. Nat Genet, 23, 18-20.
  5. Chen L, Carter-Su C (2004). Adapter protein SH2-B beta undergoes nucleocytoplasmic shuttling: implications for nerve growth factor induction of neuronal differentiation. Mol Cell Biol, 24, 3633-47. https://doi.org/10.1128/MCB.24.9.3633-3647.2004
  6. Chesi M, Nardini E, Brents LA, et al (1997). Frequent translocation t (4;14) (p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3. Nat Genet, 16, 260-4. https://doi.org/10.1038/ng0797-260
  7. Cosaceanu D, Carapancea M, Castro J, et al (2005). Modulation of response to radiation of human lung cancer cells following insulin-like growth factor-1 receptor inactivation. Cancer Lett, 222, 173-81. https://doi.org/10.1016/j.canlet.2004.10.002
  8. Diakonova M, Gunter DR, Herrington J and Carter-Su C (2002). SH2-Bbeta is a Rac-binding protein that regulates cell motility. J Biol Chem, 277, 10669-77. https://doi.org/10.1074/jbc.M111138200
  9. Donatello S, Fiorino A, Degl'Innocenti D, et al (2007). SH2B1beta adaptor is a key enhancer of RET tyrosine kinase signaling. Oncogene, 26, 6546-59. https://doi.org/10.1038/sj.onc.1210480
  10. Duan C, Li M, Rui L (2004). SH2-B promotes insulin receptor substrate 1 (IRS1)- and IRS2-mediated activation of the phosphatidylinositol 3-kinase pathway in response to leptin. J Biol Chem, 279, 43684-91. https://doi.org/10.1074/jbc.M408495200
  11. Eggert A, Ikegaki N, Liu X, et al (2000). Molecular dissection of TrkA signal transduction pathways mediating differentiation in human neuroblastoma cells. Oncogene, 19, 2043-51. https://doi.org/10.1038/sj.onc.1203518
  12. Favoni RE , de Cupis A, Ravera F, et al (1994). Expression and function of the insulin-like growth factor I system in human non-small-cell lung cancer and normal lung cell lines. Int J Cancer, 56, 858-66. https://doi.org/10.1002/ijc.2910560618
  13. Firedman E, Gejman PV, Martin GA, McCormick F (1993). Nonsense mutations in the C-terminal SH2 region of the GTPase actvating protein (GAP) gene in human tumours. Nat Genet, 5, 242-7. https://doi.org/10.1038/ng1193-242
  14. Fisseler-Eckhoff A (2009). [New TNM classification of malignant lung tumors 2009 from a pathology perspective]. Pathologe, 30, 193-9.
  15. Garcia R, Jove R (1998). Activation of STAT transcription factors in oncogenic tyrosine kinase signaling. J Biomed Sci, 5, 79-85. https://doi.org/10.1007/BF02258360
  16. Herrington J, Diakonova M, Rui L, et al (2000). SH2-B is required for growth hormone-induced actin reorganization. J Biol Chem, 275, 13126-33. https://doi.org/10.1074/jbc.275.17.13126
  17. Hua JJ, Pan WF , Jiang J, et al (2010). Expression and significance of SH2-B in ovarian serous carcinoma. Cancer Res Prev Treat, 37, 693-5 (in Chinese).
  18. Huang DM, Li JG, Chen Y, et al (2010). SH2-B enhances proliferation of colon cancer HT 229 cells. [in Chinese] Chinese J General Surg, 19, 769-73.
  19. Iseki M, Takaki S, Takatsu K (2000). Molecular cloning of the mouse APS as a member of the Lnk family adaptor proteins. Biochem Biophys Res Commun, 272, 45-54. https://doi.org/10.1006/bbrc.2000.2736
  20. Ju YS, Lee WC, Shin JY, et al (2012). A transforming KIF5B and RET gene fusion in lung adenocarcinoma revealed from whole-genome and transcriptome sequencing. Genome Res, 22, 436-45. https://doi.org/10.1101/gr.133645.111
  21. Kong M, Wang CS, Donoghue DJ (2002). Interaction of fibroblast growth factor receptor 3 and the adapter protein SH2-B. A role in STAT5 activation. J Biol Chem, 277, 15962-70. https://doi.org/10.1074/jbc.M102777200
  22. Koukourakis MI, Giatromanolaki A, O'Byme KJ, et al (1997). Platelet-derived endothelial cell growth factor expression correlates with tumour angiogenesis and prognosis in nonsmall-cell lung cancer. Br J Cancer, 75, 477-81. https://doi.org/10.1038/bjc.1997.83
  23. Lacronique V, Boureux A, Valle VD, et al (1997). A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia. Science, 278, 1309-12. https://doi.org/10.1126/science.278.5341.1309
  24. Li JG, Hua JJ, Huang DM, et al (2010). SH2-B expression in colon cancer and its clinical significance. China J Modern Med, 20, 2004-7 (in Chinese).
  25. Oneyama C, Ikeda J, Okuzaki D, et al (2011). MicroRNAmediated downregulation of mTOR/FGFR3 controls tumor growth induced by Src-related oncogenic pathways. Oncogene, 30, 3489-501. https://doi.org/10.1038/onc.2011.63
  26. Osborne MA, Dalton S, Kochan JP (1995). The yeast tribrid system-genetic detection of trans-phosphorylated ITAMSH2- interactions. Biotechnology, 13, 1474-8. https://doi.org/10.1038/nbt1295-1474
  27. Pawson T, Scott JD (1997). Signaling through scaffold,anchoring and adaptor proteins. Science, 278, 2075-80. https://doi.org/10.1126/science.278.5346.2075
  28. Qian X, Riccio A, Zhang Y, Ginty DD (1998). Identification and characterization of novel substrates of Trk receptors in developing neurons. Neuron, 21, 1017-29. https://doi.org/10.1016/S0896-6273(00)80620-0
  29. Reddy C, Chilla D, Boltax J (2011). Lung cancer screening: a review of available data and current guidelines. Hosp Pract, 39, 107-12.
  30. Ren D, Li M, Duan C, Rui L (2005). Identification of SH2-B as a key regulator of leptin sensitivity, energy balance and body weight in mice. Cell Metab, 2, 95-104. https://doi.org/10.1016/j.cmet.2005.07.004
  31. Riedel H, Yousaf N, Zhao Y, et al (2000). PSM, a mediator of PDGF-BB-, IGF-I-, and insulin-stimulated mitogenesis. Oncogene, 19, 39-50. https://doi.org/10.1038/sj.onc.1203253
  32. Rui L, Herrington J, Carter-Su C (1999). SH2-B, a membraneassociated adapter, is phosphorylated on multiple serines/ threonines in response to nerve growth factor by kinases within the MEK/ERK cascade. J Biol Chem, 274, 26485-92. https://doi.org/10.1074/jbc.274.37.26485
  33. Rui L, Mathews LS, Hotta K, et al (1997). Identification of SH2-Bbeta as a substrate of the tyrosine kinase JAK2 involved in growth hormone signaling. Mol Cell Biol, 17, 6633-44. https://doi.org/10.1128/MCB.17.11.6633
  34. Seki Y, Suzuki N, Imaizumi M, et al (2004). STAT3 and MAPK in human lung cancer tissues and suppression of oncogenic growth by JAB and dominant negative STAT. Int J Oncol, 24, 931-4.
  35. Soderdahl G, Betsholtz C, Johanson A, et al (1998). Differential expression of platelet-derived growth factor and tranforming growth factor genes in small-and non-small cell human lung carcinoma line. Int J Cancer, 41, 636-41.
  36. Somasundar P, McFadden DW, Hileman SM, Vona-Davis L (2004). Leptin is a growth factor in cancer. J Surg Res, 116, 337-49. https://doi.org/10.1016/j.jss.2003.09.004
  37. Suzuki K, Mizutani M, Hitomi Y, et al (2002). Association of SH2-B to phosphorylated tyrosine residues in the activation loop of TrkB. Res Commun Mol Pathol Pharmacol, 111, 27-39.
  38. Tang FQ , Li JG, Chen Y, et al (2011). Relationship of SH2-B and motility and invasion of colon cancer cells . Chin J Cancer Prev Treat, 18, 1-4 (in Chinese).
  39. Tanizaki J, Okamoto I, Sakai K and Nakagawa K (2011). Differential roles of trans-phosphorylated EGFR, HER2, HER3, and RET as heterodimerisation partners of MET in lung cancer with MET amplification. Br J Cancer, 105, 807-13. https://doi.org/10.1038/bjc.2011.322
  40. Tsuchiya T, Shimizu H, Horie T, Mori M (1999). Expression of leptin receptor in lung: leptin as a growth factor. Eur J Pharmacol, 365, 273-9. https://doi.org/10.1016/S0014-2999(98)00884-X
  41. Wang J, Riedel H (1998). Insulin-like growth factor-I receptor and insulin receptor association with a Src homology-2 domain-containing putative adapter. J Biol Chem, 273, 3136-9. https://doi.org/10.1074/jbc.273.6.3136
  42. Wang X, Chen L, Maures TJ, et al (2004). SH2-B is a positive regulator of nerve growth factor-mediated activation of the Akt/Forkhead pathway in PC12 Cells. J Biol Chem, 279, 133-41. https://doi.org/10.1074/jbc.M310040200
  43. Yousaf N, Deng Y, Kang Y, Riedel H (2001). Four PSM/SH2-B alternative splice variants and their differential roles in mitogenesis. J Biol Chem, 276, 40940-8. https://doi.org/10.1074/jbc.M104191200
  44. Zhang CF, Chen W, Huang QH, et al (2009). The expression of SH2-B in nonsmall-cell lung cancer. Chin J Exp Surg, 26, 1360-2 (in Chinese).
  45. Zhang X, Zhang J, Wang L, et al (2007). Therapeutic effects of STAT3 decoy oligodeoxynucleotide on human lung cancer in xenograft mice. BMC Cancer, 7, 149. https://doi.org/10.1186/1471-2407-7-149
  46. Zhang Y, Zhu W, Wang YG, et al (2006). Interaction of SH2-Bbeta with RET is involved in signaling of GDNF-induced neurite outgrowth. J Cell Sci, 119, 1666-76. https://doi.org/10.1242/jcs.02845
  47. Zhou SY, Cantley LC (2004). ZIP codes for delivering SH2 domains. Cell, 116, 41-3. https://doi.org/10.1016/S0092-8674(04)00041-8

피인용 문헌

  1. XB130—A Novel Adaptor Protein: Gene, Function, and Roles in Tumorigenesis vol.2014, pp.2090-908X, 2014, https://doi.org/10.1155/2014/903014
  2. SH2B1 promotes NSCLC cell proliferation through PI3K/Akt/mTOR signaling cascade vol.18, pp.1, 2018, https://doi.org/10.1186/s12935-018-0632-x