Amplification and overexpression of CTTN (EMS1) contribute to the metastasis of esophageal squamous cell carcinoma by promoting cell migration and anoikis resistance.
Gain of chromosome 11q13 is a common event in esophageal squamous cell carcinoma (ESCC). The cortactin gene (CTTN, also EMS1), located at 11q13, plays a pivotal role in coupling membrane dynamics to cortical actin assembly. This gene has been implicated in the motility of several types of cells. In the present study, we found that the amplification and overexpression of the CTTN gene was associated with lymph node metastasis in ESCC. Functional analysis by small interfering RNA-mediated silencing of CTTN revealed that in addition to the effect on cell migration, CTTN influenced cell invasiveness by anoikis resistance. In vivo assay showed that inhibition of CTTN expression also decreased tumor growth and lung metastasis of ESCC cells. At the molecular level, we showed for the first time that the protective role of CTTN in anoikis resistance was correlated with the activation of the phosphatidylinositol 3-kinase/Akt pathway. Overall, the data suggest that CTTN is an oncogene in the 11q13 amplicon and exerts functions on tumor metastasis in ESCC.
Luo
Man-Li
ML
State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Shen
Xiao-Ming
XM
Zhang
Yu
Y
Wei
Fang
F
Xu
Xin
X
Cai
Yan
Y
Zhang
Xun
X
Sun
Yun-Tian
YT
Zhan
Qi-Min
QM
Wu
Min
M
Wang
Ming-Rong
MR
D023102:Anoikis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D002465:Cell Movement; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D051356:Cortactin / Q000235:genetics*; D017931:DNA Primers; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009362:Neoplasm Metastasis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction
C495868:CTTN protein, human; D051356:Cortactin; D017931:DNA Primers; D012334:RNA, Neoplasm