AUTHOR=Zhang Ruijie , Li Shengjin , Lan Jian , Li Changyi , Du Xianzhi , Dong Weijie , Yu Qian , Wang Daoxin 

TITLE=CNTN-1 Upregulation Induced by Low-Dose Cisplatin Promotes Malignant Progression of Lung Adenocarcinoma Cells via Activation of Epithelial-Mesenchymal Transition

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.891665

DOI=10.3389/fgene.2022.891665

ISSN=1664-8021

ABSTRACT=<p>Tumor metastasis and invasion are the main impediments to lung adenocarcinoma successful treatment. Previous studies demonstrate that chemotherapeutic agents can elevate the malignancy of cancer cells other than their therapeutic effects. In this study, the effects of transient low-dose cisplatin treatment on the malignant development of lung adenocarcinoma cells (A549) were detected, and the underlying epigenetic mechanisms were investigated. The findings showed that A549 cells exhibited epithelial-mesenchymal transition (EMT)-like phenotype along with malignant progression under the transient low-dose cisplatin treatment. Meanwhile, low-dose cisplatin was found to induce contactin-1 (<italic>CNTN-1</italic>) upregulation in A549 cells. Subsequently, we found that further overexpressing <italic>CNTN</italic>-1 in A549 cells obviously activated the EMT process <italic>in vitro</italic> and <italic>in vivo</italic>, and caused malignant development of A549 cells <italic>in vitro</italic>. Taken together, we conclude that low-dose cisplatin can activate the EMT process and resulting malignant progression through upregulating <italic>CNTN-1</italic> in A549 cells. The findings provided new evidence that a low concentration of chemotherapeutic agents could facilitate the malignancy of carcinoma cells <italic>via</italic> activating the EMT process other than their therapeutic effects.</p>