FOXQ1 promotes esophageal cancer proliferation and metastasis by negatively modulating CDH1.
BACKGROUND
Esophageal squamous cell carcinoma (ESCC) is an aggressive tumor with rapid progression, high recurrence and metastasis rate. Besides, the 5-year survival rate of ESCC remains dismal despite improvements in treatments having developed a lot. That is because the cellular basis of ESCC has not yet been fully understood. Forkhead box family membranes possess various kinds of properties as they mediate apoptosis, cell cycle arrest, autophagy, senescence and so on. Foxhead box Q1 (FOXQ1), which has a major impact on several kinds of tumor forming and metastasis, while whether it triggers ESCC remains largely obscure.


METHODS
To determine whether aberrant FOXQ1 expression in esophageal cancer, protein level and mRNA level of specimens of cancerous tissues and adjacent non-cancerous tissues were determined by western blot and real-time PCR. Then we overexpressed or knockdowned FOXQ1 in EC9706 cell; cell growth curve and colony formation were analyzed. Cell invasion ability was analyzed by migration chambers. Reporter gene assay was used to study the transcriptional regulation activity.


RESULTS
FOXQ1 was highly expressed in esophageal cancerous tissues compared with adjacent non-cancerous tissues. FOXQ1 overexpression promotes ESCC tumor cell proliferation, whereas FOXQ1 silencing prevents ESCC tumor cell proliferation. FOXQ1 promotes ESCC metastasis via negatively modulation CDH1. CDH1 silencing could rescue the migratory ability which was blemished by FOXQ1 silencing. FOXQ1 could act as transcriptional repressor which binds to the promoter of CDH1 and blocks its transcription.


CONCLUSIONS
In this study, we identified FOXQ1 as an oncogene to promote ESCC tumor cell proliferation and metastasis by negatively regulating CDH1 in EC9706 cell. Besides, we deciphered a previously unidentified mechanism of ESCC progression and metastasis.
Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Yangqing
Y
Pei
Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Pan
P
Wang
Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Hongchun
H
Liu
Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Fucheng
F
He
Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. Electronic address: mingliang3072@163.com.
Liang
L
Ming
D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D051858:Forkhead Transcription Factors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D057809:HEK293 Cells; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
D004268:DNA-Binding Proteins; C484579:FOXQ1 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D004265:DNA Helicases; C080359:CHD1 protein, human
CDH1; ESCC; FOXQ1; Tumor metastasis