The present study was designed to explore whether BFD antagonized EMT via blocking TGF-β1-induced signaling pathway, and then help contribute to create a relatively steady microenvironment for confining lung cancer.
To identify determinants of plasticity in lung cancer we exposed eight different cell lines to TGFβ1 to induce EMT and stimulate modulation of CD133(+) CICs.
High SPARC mRNA expression in lung cancer tissues could inhibit the progression of lung cancer, while high TGFβ1 mRNA expression can promote the progression of lung cancer and participate in the metastasis of lung cancer.
In this study, we found that sFRP1 was dramatically downregulated in transforming growth factor β1 (TGF-β1)-induced EMT in the A549 human lung cancer cell line.
To test this hypothesis, we investigated the association of the TGF-beta1 -509C > T and 869T > C (L10P) polymorphisms and their haplotypes with the risk of lung cancer in a Korean population.
However, for TGF-β1 T + 869C, subgroup analysis showed no correlation between the T + 869C polymorphism and lung cancer susceptibility in patients with NSCLC.
This analysis in subpopulations of a lung cancer cell line indicated that the highly metastatic potential of lung cancer may be induced not by an alteration in the expression of a single gene, but by the accumulation of alterations in the expression of several genes involved in extracellular matrix (ECM) adhesion disruption, ECM degradation, escape from apoptosis, and resistance to transforming growth factor-beta(1) (TGF-beta(1)).
In conclusion, this study suggests that heavy smokers in this Korean population who have specific polymorphic variants, which have been associated with increased transcriptional activity of TGFB1, might be more vulnerable to lung cancer.
Overall, no significant association was found between the TGFβ1T+869C polymorphism and lung cancer susceptibility under any genetic models in the total population (p > 0.05).
We also observed long-term TGFβ1 exposure leads to an enrichment of a sub-population of CD44<sup>+</sup> CD90<sup>+</sup> cells which represent CSCs in lung cancer cells.
Finally, exposing A549 cells stably expressing ACE2 to DX600, an inhibitor of ACE2, recovered the sensitivity of lung cancer cells to TGF-β1-mediated induction of EMT.
Inhibition of transforming growth factor-β1 (TGF-β1) using LY364947 and LY2109761 has been demonstrated to radiosensitize cancer cells such as breast cancer, glioblastoma, and lung cancer.