Tumor Biology

, Volume 35, Issue 6, pp 5695–5700 | Cite as

RETRACTED ARTICLE: The association of Crk-like adapter protein with poor prognosis in glioma patients

  • Chengjun Yao
  • Shunzeng Lv
  • Mingzhi Han
  • Jie Zhang
  • Ya Zhang
  • Li Zhang
  • Ruiyang Yi
  • Dongxiao Zhuang
  • Jinsong Wu
Research Article


Glioma is the most common of brain tumors that greatly affects patient survival. In our precious study, Crk-like adapter protein (CrkL) was identified as a key regulator in glioblastoma development [1]. Here, we aimed to investigate the correlation of CrkL with patient prognosis as well as pathological indicators. Immunohistochemistry was available to evaluate CrkL expression in 49 gliomas of distinct malignancy grade, and positive stained sites were analyzed. CrkL protein was detected in cell lines by Western blot as well. We observed CrkL protein stained in 59.2 % (29 out of 49) of all glioma tissues, including 41.4 % of low-grade (I + II) gliomas, and 85.0 % of high-grade (III + IV) gliomas. Of four grades, grade IV exhibited the highest CrkL level. CrkL protein was also identified in cell lines NHA, U87, U251, T98G, and A172 by Western blot. On the other hand, CrkL expression was significantly associated with the patient’s age and WHO grade, and patients with high CrkL expression had a significantly shorter median survival time (17 months) than those (median survival time 52 months) with low CrkL expression (p < 0.001). According to Cox regression, CrkL can be suggested as an independent prognostic factor. In conclusion, CrkL is differently expressed in different grades of gliomas, and correlated to WHO grade. CrkL also independently indicates poor prognosis in old glioma patients, which can further be recommended as an effective prognostic biomarker or therapeutic target.


CrkL Immunohistochemistry Glioma Prognosis 



This study was supported by the National Key Basic Research Program of China (No. 2013CB932502), and the National Natural Science Foundation of China (No. 81171295). We greatly thank Ranran Shi in Sandy Lab for valuable suggestions.

Conflicts of interest

The authors state that there are no conflicts of interest to disclose.


  1. 1.
    Lv S, Qin J, Yi R, Coreman M, Shi R, Kang H, et al. Crkl efficiently mediates cell proliferation, migration, and invasion induced by TGF-β pathway in glioblastoma. J Mol Neurosci. 2013;51:1046–51.CrossRefPubMedGoogle Scholar
  2. 2.
    Butowski NA, Chang SM. Glial tumors: the current state of scientific knowledge. Clin Neurosurg. 2006;53:106–13.PubMedGoogle Scholar
  3. 3.
    Kleihues P, Sobin LH. World Health Organization classification of tumors. Cancer. 2000;88:2887.CrossRefPubMedGoogle Scholar
  4. 4.
    Ohgaki H, Kleihues P. Epidemiology and etiology of gliomas. Acta Neuropathol. 2005;109:93–108.CrossRefPubMedGoogle Scholar
  5. 5.
    Feller SM. Crk family adaptors-signalling complex formation and biological roles. Oncogene. 2001;20:6348–71.CrossRefPubMedGoogle Scholar
  6. 6.
    Sriram G, Birge RB. Emerging roles for Crk in human cancer. Genes Cancer. 2010;1:1132–9.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Yanagi H, Wang L, Nishihara H, Kimura T, Tanino M, Yanagi T, et al. CRKL plays a pivotal role in tumorigenesis of head and neck squamous cell carcinoma through the regulation of cell adhesion. Biochem Biophys Res Commun. 2012;418:104–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Birge RB, Kalodimos C, Inagaki F, Tanaka S. Crk and CrkL adaptor proteins: networks for physiological and pathological signaling. Cell Commun Signal. 2009;7:13.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Zhao T, Miao Z, Wang Z, Xu Y, Wu J, Liu X, et al. Overexpression of CRKL correlates with malignant cell proliferation in breast cancer. Tumour Biol. 2013;34:2891–7.CrossRefPubMedGoogle Scholar
  10. 10.
    Wang Y, Dong QZ, Fu L, Stoecker M, Wang E, Wang EH. Overexpression of Crkl correlates with poor prognosis and cell proliferation in non-small cell lung cancer. Mol Carcinog. 2013;52:890–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Cheung HW, Du J, Boehm JS, He F, Weir BA, Wang X, et al. Amplification of CRKL induces transformation and epidermal growth factor receptor inhibitor resistance in human non-small cell lung cancers. Cancer Discov. 2011;1:608–25.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Wang J, Che YL, Li G, Liu B, Shen TM, Wang H, et al. Crk and CrkL present with different expression and significance in epithelial ovarian carcinoma. Mol Carcinog. 2011;50:506–15.CrossRefPubMedGoogle Scholar
  13. 13.
    Chiu ST, Chang KJ, Ting CH, Shen HC, Li H, Hsieh FJ. Over-expression of EphB3 enhances cell-cell contacts and suppresses tumor growth in HT-29 human colon cancer cells. Carcinogenesis. 2009;30:1475–86.CrossRefPubMedGoogle Scholar
  14. 14.
    Hernández-Boluda JC, Cervantes F. Prognostic factors in chronic myeloid leukaemia. Best Pract Res Clin Haematol. 2009;22:343–53.CrossRefPubMedGoogle Scholar
  15. 15.
    Evren S, Ma XZ, Sakac D, Branch DR. SHP-1 protein tyrosine phosphatase associates with the adaptor protein CrkL. Exp Hematol. 2012;40:1055–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Singer CF, Hudelist G, Lamm W, Mueller R, Handl C, Kubista E, et al. Active (p)CrkL is overexpressed in human malignancies: potential role as a surrogate parameter for therapeutic tyrosine kinase inhibition. Oncol Rep. 2006;15:353–9.PubMedGoogle Scholar
  17. 17.
    Bell ES, Park M. Models of Crk adaptor proteins in cancer. Genes Cancer. 2012;3:341–52.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Kobashigawa Y, Sakai M, Naito M, Yokochi M, Kumeta H, Makino Y, et al. Structural basis for the transforming activity of human cancer-related signaling adaptor protein CRK. Nat Struct Mol Biol. 2007;14:503–10.CrossRefPubMedGoogle Scholar
  19. 19.
    Graf R, Barbero S, Keller N, Chen L, Uryu S, Schlaepfer D, et al. Src-inducible association of CrkL with procaspase-8 promotes cell migration. Cell Adh Migr. 2013;7:362–9.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Liu CH, Chen TC, Chau GY, Jan YH, Chen CH, Hsu CN, et al. Analysis of protein-protein interactions in cross-talk pathways reveals CRKL protein as a novel prognostic marker in hepatocellular carcinoma. Mol Cell Proteomics. 2013;12:1335–49.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Kim YH, Kwei KA, Girard L, Salari K, Kao J, Pacyna-Gengelbach M, et al. Genomic and functional analysis identifies CRKL as an oncogene amplified in lung cancer. Oncogene. 2010;29:1421–30.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Chengjun Yao
    • 1
  • Shunzeng Lv
    • 2
    • 4
  • Mingzhi Han
    • 2
  • Jie Zhang
    • 3
    • 4
  • Ya Zhang
    • 5
  • Li Zhang
    • 2
    • 4
  • Ruiyang Yi
    • 6
  • Dongxiao Zhuang
    • 1
  • Jinsong Wu
    • 1
  1. 1.Neurological Surgery Department, Glioma Surgery Division, Huashan Hospital, Shanghai Medical CollegeFudan UniversityShanghaiChina
  2. 2.Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research InstituteShandong UniversityJinanChina
  3. 3.The First Clinical College of Nanjing Medical UniversityNanjingChina
  4. 4.Department of Neurosurgery, Peking Union Medical College HospitalChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
  5. 5.Department of HematologyShandong Provincial Hospital Affiliated to Shandong UniversityJinanChina
  6. 6.Biological Sciences DivisionUniversity of ChicagoChicagoUSA

Personalised recommendations