title: Overexpression of Srcin1 contributes to the growth and metastasis of colorectal cancer.
abstract: The adaptor protein Srcin1 is a novel Src-binding protein that regulates Src activation through C-terminal Src kinase (Csk). Srcin1 behaves as a tumour suppressor in breast cancer, but the role of Srcin1 in the development of colorectal cancer (CRC) remains unknown. In the present study, Srcin1 expression in normal tissue was examined by tissue microarray and assessed by immunohistochemistry in 10 patients. In addition, the biological impact of Srcin1 knockdown on CRC cells was investigated in vitro and in vivo. The results showed that Srcin1 was expressed in different types of normal human tissues, whereas its expression was increased in human CRC tissues. Srcin1 expression also correlated with tumour progression. The suppression of Srcin1 induced cell differentiation and G0/G1 cell cycle arrest. Furthermore, Srcin1 increased cell growth as well as the capacity of migration and invasion in CRC cells. Srcin1 induced the activation of the Wnt/β-catenin signalling pathway. Moreover, Srcin1 suppression sensitized cancer cells to 5-fluorouracil (5-FU)-induced apoptosis in vitro and in vivo. Together, these results demonstrate that Srcin1 contributes to CRC carcinogenesis, invasion and metastasis. These findings provide a rationale for a mechanistic approach to CRC treatment based on the development of Srcin1-targeted therapies.
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Mengnan
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ma
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Ruyi
authors.initials: R
authors.lastname: Xie
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Meiyan
authors.initials: M
authors.lastname: Wu
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Rheumatism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Jinjun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Kequan
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Side
authors.initials: S
authors.lastname: Liu
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Jide
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Chen
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000096:biosynthesis* / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D000081247:CSK Tyrosine-Protein Kinase; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009362:Neoplasm Metastasis; D046888:Tissue Array Analysis; D060449:Wnt Signaling Pathway / Q000235:genetics; D019061:src-Family Kinases / Q000235:genetics
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C532615:SRCIN1 protein, human; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human