SATB1 protein is associated with the epithelial-mesenchymal transition process in non-small cell lung cancers

Lung cancer is one of the most frequently diagnosed neoplasms and the leading cause of cancer-related mortality worldwide. Its predominant subtype is non-small cell lung cancer (NSCLC), which accounts for over 80% of the cases. Surprisingly, the majority of lung cancer-related deaths are caused not by a primary tumour itself, but by its metastasis to distant organs. Therefore, it becomes especially important to identify the factors involved in lung cancer metastatic spread. Special AT-rich binding protein 1 (SATB1) is a nuclear matrix protein that mediates chromatin looping and plays the role of global transcriptional regulator. During the past decade, it has received much attention as a factor promoting tumour invasion. In breast, colorectal and prostate cancers, SATB1 has been shown to influence the epithelial-mesenchymal transition (EMT) process, which is thought to be crucial for cancer metastasis. The aim of this study was to analyse the possible correlations between the expression of SATB1 and major EMT-associated proteins in NSCLC clinical samples. Additionally, the impact of EMT induction in NSCLC cell lines on SATB1 mRNA expression was also investigated. Immunohistochemistry was used to assess the expression of SATB1, SNAIL, SLUG, Twist1, E-cadherin, and N-cadherin in 242 lung cancer clinical samples. EMT was induced by TGF-beta 1 treatment in the A549 and NCI-H1703 lung cancer cell lines. Changes in gene expression profiles were analyzed using real-time PCR and Droplet Digital PCR. SATB1 expression was positively correlated with the expression of SNAIL (R=0.129; P=0.045), SLUG (R=0.449; P<0.0001), and Twist1 (R=0.264; P<0.0001). Moreover, SATB1 expression significantly increased after in vitro EMT induction in A549 and NCI-H1703 cell lines. The results obtained may point to the role of SATB1 as one of the regulators of EMT in NSCLC.

Automated summary

SATB1, a nuclear matrix protein, has been identified as a factor promoting tumor invasion in lung cancer. Its expression is positively correlated with EMT-associated proteins and significantly increases after EMT induction in NSCLC cell lines. The results suggest that SATB1 may act as a regulator of EMT in NSCLC.