title: Overexpression of SRC-3 promotes esophageal squamous cell carcinoma aggressiveness by enhancing cell growth and invasiveness.
abstract: Steroid receptor coactivator-3 (SRC-3), a transcriptional coactivator for nuclear receptors and other transcription factors, plays an important role in the genesis and progression of several cancers. However, studies investigated the role of SRC-3 in esophageal squamous cell carcinomas (ESCCs) are limited, and the role of SRC-3 in tumor progression remains unclear. We examined the expression of SRC-3 in 8 ESCC cell lines and 302 human ESCC tissues by qPCR, Western blot, and immunohistochemistry. In addition, ESCC cell lines were subjected to proliferation and invasion assays, tumorigenicity assay, flow cytometry assay, qPCR, Western blot, and Chromatin Immunoprecipitation assay to investigate the role of SRC-3 in cancer progression. SRC-3 was overexpressed in 48% of cases and correlated with poor overall (P = 0.0076) and progression-free (P = 0.0069) survival of surgically resected ESCC patient. Cox regression analysis revealed that SRC-3 is an independent prognostic marker. Furthermore, we found that activation of insulin-like growth factor (IGF)/AKT) was involved in the SRC-3 on the cell growth and invasiveness in two ESCC cell lines, Eca109 and EC18 cells. SRC-3 overexpression is clinically and functionally relevant to the progression of human ESCC, and might be a useful molecular target for ESCC prognosis and treatment.
authors: Department of Pathology and Laboratory Medicine, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Fang-Ping
authors: FP
authors: Xu
authors: Department of Pathology and Laboratory Medicine, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Yan-Hui
authors: YH
authors: Liu
authors: Department of Pathology and Laboratory Medicine, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Xin-Lan
authors: XL
authors: Luo
authors: Department of Pathology and Laboratory Medicine, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Fen
authors: F
authors: Zhang
authors: Department of Thoracic Surgery, Cancer Center, Guangdong General Hospital, Guangzhou, China.
authors: Hai-Yu
authors: HY
authors: Zhou
authors: Department of Pathology and Laboratory Medicine, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Yan
authors: Y
authors: Ge
authors: Department of Pathology and Laboratory Medicine, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Chao
authors: C
authors: Liu
authors: Department of Pathology and Laboratory Medicine, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Jie
authors: J
authors: Chen
authors: Department of Pathology and Laboratory Medicine, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Dong-Lan
authors: DL
authors: Luo
authors: Department of Pathology and Laboratory Medicine, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Li-Xu
authors: LX
authors: Yan
authors: Department of Pathology and Laboratory Medicine, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Ping
authors: P
authors: Mei
authors: Department of Pathology and Laboratory Medicine, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Jie
authors: J
authors: Xu
authors: Department of Pathology and Laboratory Medicine, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Heng-Guo
authors: HG
authors: Zhuang
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D056921:Nuclear Receptor Coactivator 3 / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013002:Somatomedins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D013002:Somatomedins; D056921:Nuclear Receptor Coactivator 3; D051057:Proto-Oncogene Proteins c-akt
keywords: Cell growth; cell invasion; esophageal squamous cell carcinoma; insulin-like growth factor/AKT; steroid receptor coactivator-3