title: Myeloid cell leukemia-1 promotes epithelial-mesenchymal transition of human gastric cancer cells.
abstract: Epithelial-mesenchymal transition (EMT) is a critical process that occurs during cancer progression, and cancer stem cells have been shown to acquire the EMT phenotype. Myeloid cell leukemia-1 (Mcl-1) has been implicated in cancer progression and is overexpressed in a variety of human cancers. However, the interaction between Mcl-1 and EMT in human gastric cancer (GC) is unclear. We investigated the impact of Mcl-1 expression levels on EMT and the underlying signaling pathways in human GC cells. We used the human GC cell lines, AGS and SNU638, and small interfering RNAs (siRNAs) to evaluate the effects of Mcl-1 knockdown on cell adhesion, migration and invasion. Expression of Mcl-1 and other target genes was determined using reverse transcription-polymerase chain reaction assays and western blotting. The results revealed that expression levels of Mcl-1 mRNA and protein in the AGS and SNU638 cells were reduced following transfection with Mcl-1 siRNAs. Knockdown of Mcl-1 led to increased cellular adhesion to fibronectin and collagen. Expression levels of vimentin, MMP-2, MMP-9 and Snail protein were decreased following knockdown of Mcl-1. However, expression of E-cadherin was increased in the AGS cells following knockdown of Mcl-1. The expression of cancer stemness markers, such as CD44 and CD133, was not altered by knockdown of Mcl-1. Knockdown of Mcl-1 suppressed tumor cell migration and invasion in both human GC cell lines. Signaling cascades, including the β-catenin, MEK1/2, ERK1/2 and p38 pathways, were significantly blocked by knockdown of Mcl-1. Our results indicate that Mcl-1 expression induces EMT via β-catenin, MEK1/2 and MAPK signaling pathways, which subsequently stimulates the invasive and migratory capacity of human GC cells.
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.
authors.forename: Wan-Sik
authors.initials: WS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.
authors.forename: Nuri
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.
authors.forename: Young-Ran
authors.initials: YR
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.
authors.forename: Hyung-Hoon
authors.initials: HH
authors.lastname: Oh
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.
authors.forename: Eun
authors.initials: E
authors.lastname: Myung
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.
authors.forename: Seung-Hun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.
authors.forename: Hyung-Min
authors.initials: HM
authors.lastname: Yu
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.
authors.forename: Chan-Young
authors.initials: CY
authors.lastname: Oak
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.
authors.forename: Cho-Yun
authors.initials: CY
authors.lastname: Chung
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.
authors.forename: Hyung-Chul
authors.initials: HC
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.
authors.forename: Dae-Seong
authors.initials: DS
authors.lastname: Myung
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.
authors.forename: Sung-Bum
authors.initials: SB
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Joo
mesh_terms: D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein