title: All-Trans Retinoic Acid Inhibits Human Colorectal Cancer Cells RKO Migration via Downregulating Myosin Light Chain Kinase Expression through MAPK Signaling Pathway.
abstract: All-trans-retinoic acid (ATRA) inhibits the invasive and metastatic potentials of various cancer cells. However, the underlying mechanism is unclear. Here, we demonstrate that ATRA inhibited colorectal cancer cells RKO (human colon adenocarcinoma cell) migration by downregulating cell movement and increasing cell adhesion. ATRA inhibited the expression and activation of myosin light chain kinase (MLCK) in RKO cells, while the expression level of MLC phosphatase (MLCP) had no change in RKO cells treated with or without ATRA. The expression and activity of MLC was also inhibited in RKO cells exposed to ATRA. Intriguingly, ATRA increased the expression of occludin messenger RNA (mRNA) and protein and its localization on cell membrane. However, ATRA did not change the expression of zonula occludens 1 (ZO-1), but increased the accumulation of ZO-1 on RKO cells membrane. ML-7, an inhibitor of MLCK, significantly inhibited RKO cell migration. Furthermore, knockdown of endogenous MLCK expression inhibited RKO migration. Mechanistically, we showed that MAPK-specific inhibitor PD98059 enhanced the inhibitory effect of ATRA on RKO migration. In contrast, phorbol 12-myristate 13-acetate (PMA) attenuated the effects of ATRA in RKO cells. Moreover, knocking down endogenous extracellular signal-regulated kinase (ERK) expression inhibited MLCK expression in the RKO cells. In conclusion, ATRA inhibits RKO migration by reducing MLCK expression via extracellular signal-regulated kinase 1/Mitogen-activated protein kinase (ERK1/MAPK) signaling pathway.
authors: a Laboratory of Molecular Biology and Department of Biochemistry , Key Laboratory of Anti-inflammatory and Immunological Pharmacology, Ministry of Education and Key Laboratory of Gene Resource Utilization for Severe Disease of Anhui Province, Anhui Medical University , Anhui , China.
authors: Li
authors: L
authors: Zuo
authors: a Laboratory of Molecular Biology and Department of Biochemistry , Key Laboratory of Anti-inflammatory and Immunological Pharmacology, Ministry of Education and Key Laboratory of Gene Resource Utilization for Severe Disease of Anhui Province, Anhui Medical University , Anhui , China.
authors: Xiaoping
authors: X
authors: Yang
authors: b Department of Reproductive Center , The People's Liberation Army 105 Hospital , Anhui , China.
authors: Man
authors: M
authors: Lu
authors: c Laboratory of Molecular Biology and Department of Biochemistry , Key Laboratory of Anti-inflammatory and Immunological Pharmacology, Ministry of Education and Key Laboratory of Gene Resource Utilization for Severe Disease of Anhui Province, Anhui Medical University , Anhui , China.
authors: Ruolei
authors: R
authors: Hu
authors: c Laboratory of Molecular Biology and Department of Biochemistry , Key Laboratory of Anti-inflammatory and Immunological Pharmacology, Ministry of Education and Key Laboratory of Gene Resource Utilization for Severe Disease of Anhui Province, Anhui Medical University , Anhui , China.
authors: Huaqing
authors: H
authors: Zhu
authors: c Laboratory of Molecular Biology and Department of Biochemistry , Key Laboratory of Anti-inflammatory and Immunological Pharmacology, Ministry of Education and Key Laboratory of Gene Resource Utilization for Severe Disease of Anhui Province, Anhui Medical University , Anhui , China.
authors: Sumei
authors: S
authors: Zhang
authors: c Laboratory of Molecular Biology and Department of Biochemistry , Key Laboratory of Anti-inflammatory and Immunological Pharmacology, Ministry of Education and Key Laboratory of Gene Resource Utilization for Severe Disease of Anhui Province, Anhui Medical University , Anhui , China.
authors: Qing
authors: Q
authors: Zhou
authors: d College of Pharmacy, Anhui Medical University , China.
authors: Feihu
authors: F
authors: Chen
authors: e Department of Respiratory Medicine , the First Affiliated Hospital, Anhui Medical University , Anhui , China.
authors: Shuyu
authors: S
authors: Gui
authors: f Laboratory of Molecular Biology and Department of Biochemistry , Key Laboratory of Anti-inflammatory and Immunological Pharmacology, Ministry of Education and Key Laboratory of Gene Resource Utilization for Severe Disease of Anhui Province, Anhui Medical University , Anhui , China.
authors: Yuan
authors: Y
authors: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D062793:Occludin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014212:Tretinoin / Q000494:pharmacology*; D062826:Zonula Occludens-1 Protein / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002273:Carcinogens; D009363:Neoplasm Proteins; C568985:OCLN protein, human; D062793:Occludin; D047428:Protein Kinase Inhibitors; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D014212:Tretinoin; D009219:Myosin-Light-Chain Kinase