title: Analysis of the predictive efficiency of S100P on adverse prognosis and the pathogenesis of S100P-mediated invasion and metastasis of colon adenocarcinoma.
abstract: Elevated expression of S100P has been detected in several tumor types. To analyze the potential use of S100P for the prediction of colorectal cancer (CRC) metastasis and prognosis, S100P expression was detected in 125 patients with colon adenocarcinoma by immunohistochemistry, followed by correlation and survival analysis. High S100P expression was correlated with metastasis, as demonstrated by clinically relevant data, and predicted poor survival more effectively than preoperative serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels in colon adenocarcinoma. Stable S100P knockdown CRC cell lines were established to elucidate the relationship between S100P expression and tumor progression in vitro and in vivo. S100P knockdown resulted in reductions in the invasiveness and metastasis of CRC cells. Xenograft growth in nude mice also demonstrated that down-regulated S100P dramatically inhibited peritoneal metastasis of CRC cells. S100P promoted the invasion and metastasis of CRC by activating RAGE/ERK signaling and promoting the epithelial-mesenchymal transition (EMT). RAGE was found to be crucial for S100P-mediated EMT in colon cancer. Knockdown of RAGE in S100P-overexpressing colon cancer cells dramatically suppressed EMT process. Our results indicate that overexpression of S100P is related with an invasive and metastatic phenotype of CRC which is EMT-involved and RAGE dependent.
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Shen
authors.affiliation: Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhen
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Xian-Jun
authors.initials: XJ
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: navyd999@163.com.
authors.forename: Guo-Xin
authors.initials: GX
authors.lastname: Li
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: navyd999@163.com.
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Deng
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011237:Predictive Value of Tests; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D009363:Neoplasm Proteins; C103003:S100P protein, human
keywords: Colon adenocarcinoma; RAGE; S100P; epithelial–mesenchymal transition; survival