Increased Sushi repeat-containing protein X-linked 2 is associated with progression of colorectal cancer.
Sushi repeat-containing protein X-linked 2 (SRPX2) is a novel chondroitin sulfate proteoglycan overexpressed in gastrointestinal cancer. Its role in tumor biology remains unknown. The aim of this study was to investigate the expression of SRPX2 in colorectal cancer and its potential association with cancer progression. The expression of SRPX2 and its clinicopathological significance was evaluated using immunohistochemistry in a tissue microarray including 88 colon cancer and pairing normal tissues. The impact of SRPX2 on behavior of colorectal cancer cells and possible mechanism was explored using gene transfection and silencing. Strong staining of SRPX2 was noted in 71 (80.7 %) of 88 colon cancer specimen and 30 (34.1 %) of 88 adjacent normal tissues (P < 0.001). The expression of SRPX2 was significantly correlated with histological differentiation grade (P = 0.003), infiltration depth (P = 0.003), and clinical stage (P = 0.006). The expression of SRPX2 was significantly higher in HCT116 than in HT29 and SW480 cells. Suppression of endogenous SRPX2 expression by small interfering ribonucleic acid (siRNA) in HCT116 cells resulted in significant reduction in the ability of cell proliferation, adhesion, migration, and invasion. Up-regulation of endogenous SRPX2 in SW480 cells significantly promoted the migration and invasion of SW480 cells. In addition, inhibition of SRPX2 by siRNA led to notable down-regulation of β-catenin, matrix metalloproteinase (MMP)-2, and MMP-9. These findings indicate that overexpressed SRPX2 exerts an oncogenic role in colorectal cancer. SRPX2 may promote the invasion of colorectal cancer through MMP-2 and MMP-9 modulated by Wnt/β-catenin pathway.
Department of Gastroenterology, Beijing Shijitan Hospital, Capital Medical University, No.10, Yangfangdian, Tieyi Road, Haidian District, Beijing, 100038, China, kuikuimd@126.com.
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Liu
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Wu
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Zhou
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Fan
D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012007:Rectum / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C116881:SRPX2 protein, human