Panoply™ Human MCAM Over-expressing Stable Cell Line

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated significant efficacy against EGFR-mutant lung cancer. However, most patients treated with EGFR-TKIs have a poor prognosis due to acquired resistance. Melanoma cell adhesion molecule (MCAM), a heavily glycosylated type I transmembrane protein belonging to the immunoglobulin superfamily, is upregulated in EGFR-mutant lung adenocarcinomas resistant to EGFR-TKIs. Here, researchers demonstrate that MCAM expression levels are significantly elevated in EGFR-TKI-resistant lung adenocarcinomas compared with EGFR-TKI-sensitive lung adenocarcinomas. CCK-8 cytotoxicity assays demonstrate that overexpression of MCAM enhances EGFR-mutant lung adenocarcinoma cell resistance to EGFR-TKIs. MCAM overexpression promotes tumor growth in nude mice xenografts but has limited effect on EGFR-TKI efficacy. Furthermore, MCAM interacts with integrin β1 to activate the downstream JAK3 signaling pathway, thereby promoting EGFR-TKI resistance. The transcription factor STAT2 activates transcription of its target gene, MCAM, by binding to its promoter region. MCAM expression is regulated by the transcription factor STAT2. These studies provide a new treatment strategy for patients with EGFR-TKI resistance.

Here, researchers show that high expression of MCAM and integrin β1 is associated with lower overall survival. Co-immunoprecipitation experiments revealed an interaction between MCAM and integrin β1. Immunofluorescence experiments showed that MCAM and integrin β1 were both located on the cell membrane and colocalized in HCC827GR and HCC827OR cells. Furthermore, Western blot analysis confirmed that overexpression of MCAM increased integrin β1 expression, while knockdown of MCAM decreased integrin β1 expression. These results suggest that MCAM may activate JAK3 through integrin β1. Subsequently, the researchers transfected integrin β1 siRNA into MCAM-overexpressing cells and control cells. Western blot results showed that MCAM overexpression increased the expression of integrin β1 and p-JAK3 proteins. Knockdown of integrin β1 in MCAM-overexpressing cell lines reduced the expression of aberrantly activated integrin β1 and p-JAK3 proteins (Figure 1E). CCK-8 cytotoxicity assays also showed that reducing the expression of integrin β1 could partially rescue the EGFR-TKI resistance caused by MCAM overexpression (Figure 1C-D).

Figure 1. MCAM promotes cell resistance by activating JAK3 via an interaction with Integrin β1. (Zhang S, et al., 2025)