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01.12.2012 | Research | Ausgabe 1/2012 Open Access

Molecular Cancer 1/2012

Lyn is involved in CD24-induced ERK1/2 activation in colorectal cancer

Zeitschrift:
Molecular Cancer > Ausgabe 1/2012
Autoren:
Ning Su, Liang Peng, Bingqing Xia, Yingying Zhao, Angao Xu, Jing Wang, Xinying Wang, Bo Jiang
Wichtige Hinweise

Electronic supplementary material

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.

Competing interests

The authors declare that they have no competing interests.

Author's Contributions

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.

Abstract

Background and aim

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.

Methods and Results

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.

Conclusions

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.
Zusatzmaterial
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)
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Authors’ original file for figure 1
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Authors’ original file for figure 2
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Authors’ original file for figure 3
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Authors’ original file for figure 4
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Authors’ original file for figure 5
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Authors’ original file for figure 6
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Literatur
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