Inhibition of TMPRSS4 mediated epithelial‐mesenchymal transition is critically involved in antimetastatic effect of melatonin in colorectal cancers. (11th June 2021)

• Record Type: Journal Article
• Authors: Oh, Bum Suk; Im, Eunji; Lee, Hyo‐Jung; Sim, Deok Yong; Park, Ji Eon; Park, Woon Yi; Park, Youngsang; Koo, Jinsuk; Pak, Ji‐Na; Kim, Dong Hee; Shim, Bum Sang; Kim, Sung‐Hoon
• Is Part Of: Phytotherapy research. Volume 35:Number 8(2021)
• Page Start: 4538
• Page End: 4546
• Publication Date: 2021-06-11
• Subjects: colorectal cancer -- EMT -- melatonin -- metastasis -- TMPRSS4; Materia medica, Vegetable -- Periodicals; Botany, Medical -- Periodicals; Medicinal plants -- Periodicals; Plant Extracts -- therapeutic use -- Periodicals; Plants, Medicinal -- Periodicals; 581.634
• DOI: 10.1002/ptr.7156
• Languages: English
• ISSNs: 0951-418X

Abstract

Abstract : In the current study, the underlying anti‐metastatic mechanism of melatonin contained in some edible plants was explored in association with transmembrane protease serine 4 (TMPRSS4) mediated metastasis and epithelial–mesenchymal transition (EMT) signaling in human HCT15 and SW620 colorectal cancer cells. Here, TMPRSS4 was highly expressed in HCT15, but was weakly expressed in SW620 cells. Melatonin exerted weak cytotoxicity, decreased invasion, adhesion, and migration, and attenuated the expression of TMPRSS4, cyclin E, pro‐urokinase‐type plasminogen activator (pro‐uPA), p‐signal transducer and activator of transcription 3 (p‐STAT3), p‐focal adhesion kinase (p‐FAK), Snail and increased the expression of E‐cadherin, p27, pp38 and p‐Jun N‐terminal kinases (p‐JNK) in HCT15 cells. Conversely, overexpression of TMPRSS4 reduced the ability of melatonin to activate E‐cadherin and reduce Snail. Furthermore, even in SW620 cells transfected with TMPRSS4‐overexpression plasmid, melatonin effectively suppressed invasion and migration along with decreased expression of Snail, cyclin A, cyclin E, pro‐uPA and p‐FAK and increased expression of E‐cadherin and p27. Overall, these findings provide evidence that melatonin suppresses metastasis in colon cancer cells via inhibition of TMPRSS4 mediated EMT.