COR-L23

Differences in Activity and Expression of STAT3 and Everolimus-Induced Expression Changes of EMT Indicators in Lung-Derived Cell Lines

Interstitial lung disease (ILD), a potentially fatal and dose-limiting toxicity, is associated with mTOR inhibitors in metastatic renal-cell carcinoma (RCC). Yamamoto et al. investigated whether STAT3 polymorphism rs4796793 (-1697C/G) influences risk of ILD and explored potential mechanisms using lung-derived cell lines.

Six lung-derived cell lines possessed unique genotypes (A549: CC, LK-2: GC, all other cell lines: GG; Fig. 1A). STAT3 expression levels were independent of genotype, although STAT3 activation (p-STAT3/total STAT3) was higher in EBC-1 and SK-MES-1 cells than in A549 cells, and no consistent pattern was observed among the lines based on genotype. Everolimus altered EMT marker expression in a cell-line dependent manner (Fig. 1C). In EBC-1, it significantly upregulated mesenchymal indicators N-cadherin and vimentin; in ABC-1, SK-MES-1, and COR-L23, it increased fibronectin; and in SK-MES-1 and COR-L23, it decreased epithelial marker E-cadherin. Notably, A549 cells showed no significant EMT changes at equivalent drug concentrations. N-cadherin and vimentin were undetectable in ABC-1 and COR-L23 by Western blot.