Inhibition of TMPRSS4 mediated epithelial-mesenchymal transition is critically involved in antimetastatic effect of melatonin in colorectal cancers.

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.

• Authors: Bum Suk Oh, Eunji Im, Hyo-Jung Lee, Deok Yong Sim, Ji Eon Park, Woon Yi Park, Youngsang Park, Jinsuk Koo, Ji-Na Pak, Dong Hee Kim, Bum Sang Shim, Sung-Hoon Kim
• Journal: Phytotherapy research : PTR (Phytother Res) Vol. 35 Issue 8 Pg. 4538-4546 (Aug 2021) ISSN: 1099-1573 [Electronic] England
• PMID: 34114707 (Publication Type: Journal Article)
• Copyright: © 2021 John Wiley & Sons Ltd.

Chemical References

• Membrane Proteins
• Serine
• Serine Endopeptidases
• TMPRSS4 protein, human
• Melatonin

Topics

• Cell Line, Tumor
• Cell Movement
• Colorectal Neoplasms (drug therapy, genetics)
• Epithelial-Mesenchymal Transition
• Gene Expression Regulation, Neoplastic
• Humans
• Melatonin (pharmacology)
• Membrane Proteins (antagonists & inhibitors)
• Serine
• Serine Endopeptidases