However, CD24 has been identified as a novel regulator selleck chem Enzalutamide of proliferation, apop tosis Inhibitors,Modulators,Libraries and invasion in human cancer. Several ligands of CD24, including P selectin and Siglec 10, have been identified and are found to be crucial for tumor development. In our previous study, we found that the activation of extracellular signal Inhibitors,Modulators,Libraries regulated kinases 1 and 2 and p38 MAPK were dependent of CD24 and required for the proliferation and invasion of CRC cells in vitro and in vivo. Although CD24 is an important player in CRC, the mechanisms of its function in CRC remain unclear. Exploring the mechanisms underlying CD24 mediated activation of MAP kinases would be beneficial in for better understanding of the role of CD24 in CRC development. To this end, the connection between CD24 and MAP kinases in literature has been studied.
Zarn et al. found that CD24 localized in glycolipid enriched membrane domains, which are the specialized areas in the plasma membrane signaling platforms, Inhibitors,Modulators,Libraries and associated with Lyn in an erythroleukemia cell line. Moreover, Petra et al. showed that CD24 interacted with c Src and promoted its activity within lipid rafts in breast cancer cells. Furthermore, many studies have suggested that Src family kinases are located upstream of MAPKs cascades in several receptor signaling systems. SFKs are a family of non receptor type tyrosine kinases and include at least nine highly homologous pro teins in mammals. Lyn is an important member of the SFKs and widely expressed in B lymphocytes and myeloid cells. Lyn establishes thresholds by acting as both a positive and negative modulator of a variety of signaling responses.
Furthermore, aberrant activa tion of Lyn has been implicated Inhibitors,Modulators,Libraries in variety of human tumors, including breast cancer, prostate cancer, glioblastoma and CRC. Therefore, we hypothesize that SFKs are involved in the CD24 induced ERK1 2 acti vation. In the present study, we examined the correlation between CD24 and Lyn in CRC. Our results revealed that CD24 interacted with Lyn and induced the activation and nuclear translocation of Lyn. In contrast, the inactivation of Lyn abrogated CD24 induced cell invasion and ERK1 2 activation in CRC cells. Analysis of CRC tis sues with immunohistochemistry staining showed that the expression of CD24 and Lyn was positively corre lated and associated with tumor stage and lymph node and distant metastasis.
Our study suggests that the expression of CD24 is associated with the activa tion of Lyn and ERK1 2, which may be a novel mech anism related to CD24 mediated regulation of CRC Inhibitors,Modulators,Libraries development. Results Lyn interacted with CD24 and was activated by CD24 in CRC cells To investigate the association of CD24 and SFKs, we exam ined the activation such information of SFKs, including Src, Lyn, Fyn and lck in SW480CD24 cells and SW480 vector and parental cells.