Therefore, we hypothesized that there was an interaction between CD24 and Lyn directly or indir ectly in CRC. Through CO IP assays, we identified this interaction in CRC, selleck inhibitor and this might be the first report of an interaction between CD24 and Lyn in solid tumors. To identify the interaction between CD24 and Lyn in vivo, we examined the expression of CD24 and Lyn by immunohistochemical staining on serial sections of CRC tissues. The results showed that the expression of CD24 was positively correlated with phospho Lyn ex pression in 202 CRC patients. Mierke et al. found that CD24 enhanced human lung cancer cell invasion through increased generation or transmission of contractile forces. In the present study, we also found that overexpression of CD24 could increase the cell invasion ability.

Furthermore, we inves tigated the role of Lyn in CD24 induced CRC cell inva sion. After treating cells with PP2, a specific inhibitor Inhibitors,Modulators,Libraries of SFKs, CD24 induced CRC cell invasion was abrogated, suggesting that Lyn was involved in CD24 induced cell invasion. SFKs are known to be ubiquitously distributed in the cell membrane, but Src is located in perinuclear membranes, endosomes and possibly even the nucleus, implicating the involvement of Src in nuclear signal transduction events. The regulation of nucleocyto plasmic distribution of Lyn contributes to the associ ation of Lyn with other upstream or downstream signaling molecules. To elucidate the underlying mechanisms in this process, Inhibitors,Modulators,Libraries we examined the subcellular localization of Lyn by immunoflourescence staining.

In SW480VEC cells, positive cellular signals of Lyn was pre dominant in the cytoplasm, and over expression of CD24 resulted in a cytosolic decrease and a nuclear ac cumulation of Lyn. The nuclear translocation strongly implied that Inhibitors,Modulators,Libraries the regulation of gene transcription of Lyn might be involved, Inhibitors,Modulators,Libraries which should be clarified in further studies. In addition, we found that Lyn and CD24 were expressed in different tumor stages of CRC and the ex pression level of CD24 and Lyn was positively correlated with tumor grade, tumor stage, invasion depth, and lymph node and distant metastasis. SFKs are the upstream modulator of MAP kinases in several receptor signaling pathways. Therefore, it is pos sible that CD24 directly or indirectly interacts with Lyn and affects the activity of ERK1 2.

We found that the de pletion of CD24 Inhibitors,Modulators,Libraries and Lyn, by specific siRNA or inactiva tion of Lyn by its specific inhibitor PP2, could reduce the phosphorylation level of ERK1 2 respectively or syn ergistically. CO IP assays showed that Lyn interacted with ERK1 2 in a CD24 high truly expression cell line and the Lyn ERK interaction was disrupted by the depletion of CD24, suggesting that Lyn was involved in CD24 induced ERK1 2 activation in CRC cells.