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Erschienen in: Tumor Biology 5/2013

01.10.2013 | Research Article

Overexpression of CRKL correlates with malignant cell proliferation in breast cancer

verfasst von: Tingting Zhao, Zhifeng Miao, Zhenning Wang, Yingying Xu, Jianhua Wu, Xingyu Liu, Yi You, Jiguang Li

Erschienen in: Tumor Biology | Ausgabe 5/2013

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Abstract

Crk-like (CRKL) is an adapter protein that has crucial roles in multiple biological processes, including cell proliferation, adhesion, and migration. However, the expression pattern of CRKL protein and its clinical significance in human breast cancers have not been well characterized. In this study, expression of CRKL was evaluated in 108 human invasive ductal carcinoma (IDC) tissues by immunohistochemistry. CRKL protein was upregulated in the cancer tissues compared with adjacent normal mammary glands. Overexpression of CRKL was found in 40 of 108 (37.03 %) breast cancer samples and correlated with advanced p-tumor–node–metastasis stage (p = 0.002), nodal metastasis (p = 0.0323), and tumor size (p = 0.0075). In addition, overexpression of CRKL in the MDA-MB-435 cell line promoted cell proliferation, and small interfering RNA knockdown of CRKL in the MDA-MB-453 cell line inhibited proliferation. Further analysis of cell cycle-related molecules showed that CRKL induced cyclin D1 and phosphorylated extracellular signal-regulated kinase expression. In conclusion, this study demonstrated that overexpression of CRKL correlated with progression and malignant proliferation of human breast cancers.
Literatur
1.
Zurück zum Zitat Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10–29.CrossRefPubMed Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10–29.CrossRefPubMed
2.
Zurück zum Zitat Kabbage M, Trimeche M, Ben Nasr H, Hammann P, Kuhn L, Hamrita B, et al. Expression of the molecular chaperone alphaB-crystallin in infiltrating ductal breast carcinomas and the significance thereof: an immunohistochemical and proteomics-based strategy. Tumour Biol. 2012;33(6):2279–88.CrossRefPubMed Kabbage M, Trimeche M, Ben Nasr H, Hammann P, Kuhn L, Hamrita B, et al. Expression of the molecular chaperone alphaB-crystallin in infiltrating ductal breast carcinomas and the significance thereof: an immunohistochemical and proteomics-based strategy. Tumour Biol. 2012;33(6):2279–88.CrossRefPubMed
3.
Zurück zum Zitat Elfagieh M, Abdalla F, Gliwan A, Boder J, Nichols W, Buhmeida A. Serum tumour markers as a diagnostic and prognostic tool in Libyan breast cancer. Tumour Biol. 2012;33(6):2371–7.CrossRefPubMed Elfagieh M, Abdalla F, Gliwan A, Boder J, Nichols W, Buhmeida A. Serum tumour markers as a diagnostic and prognostic tool in Libyan breast cancer. Tumour Biol. 2012;33(6):2371–7.CrossRefPubMed
4.
Zurück zum Zitat ten Hoeve J, Morris C, Heisterkamp N, Groffen J. Isolation and chromosomal localization of CRKL, a human crk-like gene. Oncogene. 1993;8(9):2469–74.PubMed ten Hoeve J, Morris C, Heisterkamp N, Groffen J. Isolation and chromosomal localization of CRKL, a human crk-like gene. Oncogene. 1993;8(9):2469–74.PubMed
5.
Zurück zum Zitat Feller SM. Crk family adaptors-signalling complex formation and biological roles. Oncogene. 2001;20(44):6348–71.CrossRefPubMed Feller SM. Crk family adaptors-signalling complex formation and biological roles. Oncogene. 2001;20(44):6348–71.CrossRefPubMed
6.
Zurück zum Zitat ten Hoeve J, Arlinghaus RB, Guo JQ, Heisterkamp N, Groffen J. Tyrosine phosphorylation of CRKL in Philadelphia + leukemia. Blood. 1994;84(6):1731–6.PubMed ten Hoeve J, Arlinghaus RB, Guo JQ, Heisterkamp N, Groffen J. Tyrosine phosphorylation of CRKL in Philadelphia + leukemia. Blood. 1994;84(6):1731–6.PubMed
7.
Zurück zum Zitat ten Hoeve J, Kaartinen V, Fioretos T, Haataja L, Voncken JW, Heisterkamp N, et al. Cellular interactions of CRKL, and SH2-SH3 adaptor protein. Cancer Res. 1994;54(10):2563–7.PubMed ten Hoeve J, Kaartinen V, Fioretos T, Haataja L, Voncken JW, Heisterkamp N, et al. Cellular interactions of CRKL, and SH2-SH3 adaptor protein. Cancer Res. 1994;54(10):2563–7.PubMed
8.
Zurück zum Zitat Senechal K, Halpern J, Sawyers CL. The CRKL adaptor protein transforms fibroblasts and functions in transformation by the BCR-ABL oncogene. J Biol Chem. 1996;271(38):23255–61.CrossRefPubMed Senechal K, Halpern J, Sawyers CL. The CRKL adaptor protein transforms fibroblasts and functions in transformation by the BCR-ABL oncogene. J Biol Chem. 1996;271(38):23255–61.CrossRefPubMed
9.
Zurück zum Zitat Hemmeryckx B, van Wijk A, Reichert A, Kaartinen V, de Jong R, Pattengale PK, et al. Crkl enhances leukemogenesis in BCR/ABL P190 transgenic mice. Cancer Res. 2001;61(4):1398–405.PubMed Hemmeryckx B, van Wijk A, Reichert A, Kaartinen V, de Jong R, Pattengale PK, et al. Crkl enhances leukemogenesis in BCR/ABL P190 transgenic mice. Cancer Res. 2001;61(4):1398–405.PubMed
10.
Zurück zum Zitat 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(2):353–9.PubMed 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(2):353–9.PubMed
11.
Zurück zum Zitat 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. 2011;29(10):1421–30.CrossRef 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. 2011;29(10):1421–30.CrossRef
12.
Zurück zum Zitat Ladanyi M. CRKL as a lung cancer oncogene and mediator of acquired resistance to EGFR inhibitors: is it all that it is cracked up to be? Cancer Discov. 1(7):560-1. Ladanyi M. CRKL as a lung cancer oncogene and mediator of acquired resistance to EGFR inhibitors: is it all that it is cracked up to be? Cancer Discov. 1(7):560-1.
13.
Zurück zum Zitat 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. 2012. doi:10.1002/mc.21935. 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. 2012. doi:10.​1002/​mc.​21935.
14.
Zurück zum Zitat Feller SM, Knudsen B, Wong TW, Hanafusa H. Detection of SH3-binding proteins in total cell lysates with glutathione S-transferase-SH3 fusion proteins: SH3 blot assay. Methods Enzymol. 1995;255:369–78.CrossRefPubMed Feller SM, Knudsen B, Wong TW, Hanafusa H. Detection of SH3-binding proteins in total cell lysates with glutathione S-transferase-SH3 fusion proteins: SH3 blot assay. Methods Enzymol. 1995;255:369–78.CrossRefPubMed
15.
Zurück zum Zitat Salgia R, Uemura N, Okuda K, Li JL, Pisick E, Sattler M, et al. CRKL links p210BCR/ABL with paxillin in chronic myelogenous leukemia cells. J Biol Chem. 1995;270(49):29145–50.CrossRefPubMed Salgia R, Uemura N, Okuda K, Li JL, Pisick E, Sattler M, et al. CRKL links p210BCR/ABL with paxillin in chronic myelogenous leukemia cells. J Biol Chem. 1995;270(49):29145–50.CrossRefPubMed
16.
Zurück zum Zitat Mintz PJ, Cardo-Vila M, Ozawa MG, Hajitou A, Rangel R, Guzman-Rojas L, et al. An unrecognized extracellular function for an intracellular adapter protein released from the cytoplasm into the tumor microenvironment. Proc Natl Acad Sci U S A. 2009;106(7):2182–7.PubMedCentralCrossRefPubMed Mintz PJ, Cardo-Vila M, Ozawa MG, Hajitou A, Rangel R, Guzman-Rojas L, et al. An unrecognized extracellular function for an intracellular adapter protein released from the cytoplasm into the tumor microenvironment. Proc Natl Acad Sci U S A. 2009;106(7):2182–7.PubMedCentralCrossRefPubMed
18.
Zurück zum Zitat Sebolt-Leopold JS, Herrera R. Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat Rev Cancer. 2004;4(12):937–47.CrossRefPubMed Sebolt-Leopold JS, Herrera R. Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat Rev Cancer. 2004;4(12):937–47.CrossRefPubMed
19.
Zurück zum Zitat Mirzoeva OK, Das D, Heiser LM, Bhattacharya S, Siwak D, Gendelman R, et al. Basal subtype and MAPK/ERK kinase (MEK)-phosphoinositide 3-kinase feedback signaling determine susceptibility of breast cancer cells to MEK inhibition. Cancer Res. 2009;69(2):565–72.PubMedCentralCrossRefPubMed Mirzoeva OK, Das D, Heiser LM, Bhattacharya S, Siwak D, Gendelman R, et al. Basal subtype and MAPK/ERK kinase (MEK)-phosphoinositide 3-kinase feedback signaling determine susceptibility of breast cancer cells to MEK inhibition. Cancer Res. 2009;69(2):565–72.PubMedCentralCrossRefPubMed
20.
Zurück zum Zitat Nosaka Y, Arai A, Miyasaka N, Miura O. CrkL mediates Ras-dependent activation of the Raf/ERK pathway through the guanine nucleotide exchange factor C3G in hematopoietic cells stimulated with erythropoietin or interleukin-3. J Biol Chem. 1999;274(42):30154–62.CrossRefPubMed Nosaka Y, Arai A, Miyasaka N, Miura O. CrkL mediates Ras-dependent activation of the Raf/ERK pathway through the guanine nucleotide exchange factor C3G in hematopoietic cells stimulated with erythropoietin or interleukin-3. J Biol Chem. 1999;274(42):30154–62.CrossRefPubMed
21.
Zurück zum Zitat Shi Y, Chen L, Li J, Lv YL, Sun Q, Wang LX, et al. Prognostic and predictive values of pERK1/2 and pAkt-1 expression in non-small cell lung cancer patients treated with adjuvant chemotherapy. Tumour Biol. 2011;32(2):381–90.CrossRefPubMed Shi Y, Chen L, Li J, Lv YL, Sun Q, Wang LX, et al. Prognostic and predictive values of pERK1/2 and pAkt-1 expression in non-small cell lung cancer patients treated with adjuvant chemotherapy. Tumour Biol. 2011;32(2):381–90.CrossRefPubMed
22.
Zurück zum Zitat Dong QZ, Wang Y, Tang ZP, Fu L, Li QC, Wang ED, et al. Derlin-1 is overexpressed in non-small cell lung cancer and promotes cancer cell invasion via EGFR-ERK-mediated up-regulation of MMP-2 and MMP-9. Am J Pathol. 2013;182(3):954–64.CrossRefPubMed Dong QZ, Wang Y, Tang ZP, Fu L, Li QC, Wang ED, et al. Derlin-1 is overexpressed in non-small cell lung cancer and promotes cancer cell invasion via EGFR-ERK-mediated up-regulation of MMP-2 and MMP-9. Am J Pathol. 2013;182(3):954–64.CrossRefPubMed
Metadaten
Titel
Overexpression of CRKL correlates with malignant cell proliferation in breast cancer
verfasst von
Tingting Zhao
Zhifeng Miao
Zhenning Wang
Yingying Xu
Jianhua Wu
Xingyu Liu
Yi You
Jiguang Li
Publikationsdatum
01.10.2013
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 5/2013
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-0851-7

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