The online version of this article (doi:10.1186/1476-4598-11-43) contains supplementary material, which is available to authorized users.
An erratum to this article is available at http://dx.doi.org/10.1186/1476-4598-11-68.
The authors declare that they have no competing interests.
NS and LP participated in the design of the study, and carried out the experiment, and performed the statistical analysis. BX, YZ, AX and JW participated in the experiment and drafted the manuscript. XW and BJ conceived of the study, and participated in its design and coordination and edited the manuscript. All authors read and approved the final manuscript.
CD24 expression is associated with human colorectal cancer (CRC). Our previous data indicated that CD24 promoted the proliferation and invasion of colorectal cancer cells through the activation of ERK1/2. Since Src family kinases are frequently deregulated in CRC and closely related to the MAPK signaling pathway, we investigated the impact of Lyn, an important member of SFKs, on CD24-induced ERK1/2 activation in CRC.
The interaction of CD24 and Lyn was identified by co-immunoprecipitation (Co-IP) and ectopic expression of CD24-induced Lyn activation. Inhibition of Lyn activation by phosphatase PP2 in SW480CD24cells abrogated CD24-induced invasion. The results of the Co-IP and immunofluorescence assay revealed that overexpression of CD24 enhanced the interaction of Lyn and ERK1/2 and induced the nuclear translocation of Lyn. However, inhibition of Lyn activity attenuated CD24-induced ERK1/2 activation, and depletion of CD24 disrupted Lyn-ERK1/2 interaction. Immunohistochemistry analysis for 202 cases of CRC showed that the expression of both CD24 and Lyn was positively correlated with tumor grade, stage, lymph node and distant metastasis. Patients with lower expression of CD24 or Lyn had a higher survival rate. The Cox multivariate analysis showed that CD24 expression, but not Lyn expression, was an independent prognostic factor of CRC.
Our results suggest that Lyn is involved in CD24-induced ERK1/2 activation in CRC. The expression of CD24 is associated with activation of Lyn and ERK1/2, which might be a novel mechanism related to CD24-mediated regulation of CRC development.
Additional file 1: Supplementary figures. Figure S1: Densitometry results of Figure 1A; Figure S2: CD24 siRNA-2 results; Figure S3: Means ± standard errors (SE) for three independent experiments for Figure 4. (PDF 340 KB)12943_2012_1016_MOESM1_ESM.pdf
Authors’ original file for figure 112943_2012_1016_MOESM2_ESM.pdf
Authors’ original file for figure 212943_2012_1016_MOESM3_ESM.pdf
Authors’ original file for figure 312943_2012_1016_MOESM4_ESM.pdf
Authors’ original file for figure 412943_2012_1016_MOESM5_ESM.pdf
Authors’ original file for figure 512943_2012_1016_MOESM6_ESM.pdf
Authors’ original file for figure 612943_2012_1016_MOESM7_ESM.pdf
Kristiansen G, Winzer KJ, Mayordomo E, Bellach J, Schluns K, Denkert C, Dahl E, Pilarsky C, Altevogt P, Guski H, Dietel M: CD24 expression is a new prognostic marker in breast cancer. Clin Cancer Res. 2003, 9: 4906-4913. PubMed
Bretz N, Noske A, Keller S, Erbe-Hofmann N, Schlange T, Salnikov AV, Moldenhauer G, Kristiansen G, Altevogt P: CD24 promotes tumor cell invasion by suppressing tissue factor pathway inhibitor-2 (TFPI-2) in a c-Src-dependent fashion. Clin Exp Metastasis. 2011
Friederichs J, Zeller Y, Hafezi-Moghadam A, Grone HJ, Ley K, Altevogt P: The CD24/P-selectin binding pathway initiates lung arrest of human A125 adenocarcinoma cells. Cancer Res. 2000, 60: 6714-6722. PubMed
Baumann P, Thiele W, Cremers N, Muppala S, Krachulec J, Diefenbacher M, Kassel O, Mudduluru G, Allgayer H, Frame M, Sleeman JP: CD24 interacts with and promotes the activity of c-src within lipid rafts in breast cancer cells, thereby increasing integrin-dependent adhesion. Cell Mol Life Sci. 2011
Pazdrak K, Schreiber D, Forsythe P, Justement L, Alam R: The intracellular signal transduction mechanism of interleukin 5 in eosinophils: the involvement of lyn tyrosine kinase and the Ras-Raf-1-MEK-microtubule-associated protein kinase pathway. J Exp Med. 1995, 181: 1827-1834. 10.1084/jem.181.5.1827 CrossRefPubMed
Janas ML, Hodgkin P, Hibbs M, Tarlinton D: Genetic evidence for Lyn as a negative regulator of IL-4 signaling. J Immunol. 1999, 163: 4192-4198. PubMed
Park SI, Zhang J, Phillips KA, Araujo JC, Najjar AM, Volgin AY, Gelovani JG, Kim SJ, Wang Z, Gallick GE: Targeting SRC family kinases inhibits growth and lymph node metastases of prostate cancer in an orthotopic nude mouse model. Cancer Res. 2008, 68: 3323-3333. 10.1158/0008-5472.CAN-07-2997 CrossRefPubMed
Hao JM, Chen JZ, Sui HM, Si-Ma XQ, Li GQ, Liu C, Li JL, Ding YQ, Li JM: A five-gene signature as a potential predictor of metastasis and survival in colorectal cancer. J Pathol. 2010, 220: 475-489. PubMed
Lee JH, Kim SH, Lee ES, Kim YS: CD24 overexpression in cancer development and progression: a meta-analysis. Oncol Rep. 2009, 22: 1149-1156. PubMed
Yamaguchi N, Nakayama Y, Urakami T, Suzuki S, Nakamura T, Suda T, Oku N: Overexpression of the Csk homologous kinase (Chk tyrosine kinase) induces multinucleation: a possible role for chromosome-associated Chk in chromosome dynamics. J Cell Sci. 2001, 114: 1631-1641. PubMed
Albini A, Iwamoto Y, Kleinman HK, Martin GR, Aaronson SA, Kozlowski JM, McEwan RN: A rapid in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res. 1987, 47: 3239-3245. PubMed
- Lyn is involved in CD24-induced ERK1/2 activation in colorectal cancer
- BioMed Central
Neu im Fachgebiet Onkologie
Mail Icon II