LASP1 Induces Epithelial-Mesenchymal Transition in Lung Cancer through the TGF-β1/Smad/Snail Pathway

LIM and SH3 domain protein 1 (LASP1), highly expressed in a variety of tumors, is considered as a novel tumor metastasis biomarker. However, it is unknown which signaling pathway works and how the signal transduces into cell nucleus to drive tumor progression by LASP1. The aim of this study is to explore the essential role of LASP1 in TGF-β1-induced epithelial-mesenchymal transition (EMT) in lung cancer cells.

The gene and protein levels of LASP-1 were successfully silenced or overexpressed by LASP-1 shRNA lentivirus or pcDNA in TGF-β1-treated lung cancer cell lines, respectively. Then, the cells were developed EMT by TGF-β1. The cell abilities of invasion, migration, and proliferation were measured using Transwell invasion assay, wound healing assay, and MTT assay, respectively. Western blotting was used to observe the protein levels of EMT-associated molecules, including N-cadherin, vimentin, and E-cadherin, and the key molecules in the TGF-β1/Smad/Snail signaling pathway, including pSmad2 and Smad2, pSmad3 and Smad3, and Smad7 in cell lysates, as well as Snail1, pSmad2, and pSmad3 in the nucleus.

TGF-β1 induced higher LASP1 expression. LASP1 silence and overexpression blunted or promoted cell invasion, migration, and proliferation upon TGF-β1 stimulation. LASP1 also regulated the expression of vimentin, N-cadherin, and E-cadherin in TGF-β1-treated cells. Activity of key Smad proteins (pSmad2 and pSmad3) and protein level of Smad7 were markedly regulated through LASP1. Furthermore, LASP1 affected the nuclear localizations of pSmad2, pSmad3, and Snail1.

This study reveals that LASP1 regulates the TGF-β1/Smad/Snail signaling pathway and EMT markers and features, involving in key signal molecules and their nuclear levels. Therefore, LASP1 might be a drug target in lung cancer.