Increased Sushi repeat-containing protein X-linked 2 is associated with progression of colorectal cancer

Abstract

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.

Sushi repeat-containing protein X-linked 2 promotes angiogenesis through the urokinase-type plasminogen activator receptor dependent integrin αvβ3/focal adhesion kinase pathways

“…Tanaka et al (7) reported that SRPX2 increases FAK phosphorylation levels in several gastric cancer cells. Gao et al (9) also found that the increase in SRPX2 is associated with FAK phosphorylation in pancreatic cancer tissue. In this study, FAK phosphorylation in HUVECs after addition of SRPX2 recombinant protein for 4.0 h was investigated.…”

“…The overexpression vector of pcDNA3.1(+)-SRPX2 plasmid and empty plasmid vector as control were constructed and transfected into SW480 (ATCC, Manassas, VA, USA) as previously described (8). SRPX2-CM was prepared according to Tanaka et al (10).…”

“…Western blots were performed as previously described (8). The primary antibodies involved were as following: 1:1,000 phospho-Akt (Ser473, 4060), 1:1,000 Akt (9272), 1:1,000 phospho-PI3 Kinase p85 (Tyr458)/p55 (Tyr199, 4228), 1:1,000 PI3 Kinase p85 (42571), 1:1,000 phospho-ERK1/2 (Thr202/ Tyr204, 43771), 1:1,000 ERK1/2 (4695), and the focal adhesion kinase (FAK) antibody kit (9330) including phospho-FAK (Tyr576/577) antibody, phospho-FAK (Tyr925) antibody, phospho-FAK (Tyr397) 1:2,000 antibody, FAK antibody, and 1:10,000 glyceraldehyde 3-phosphate dehydrogenase (5174).…”

“…Sushi repeat-containing protein X-linked 2 (SRPX2) is a newly demonstrated secretory CSPG (5) that is markedly increased in multiple cancers, such as gastric cancer, colorectal cancer (CRC), pancreatic cancer, and glioblastoma and correlates with a poor outcome or advanced tumor stage (5)(6)(7)(8)(9)(10). SRPX2 is also believed to have a role in angiogenesis.…”

Retracted: Knockdown of SRPX2 inhibits the proliferation, migration, and invasion of prostate cancer cells through the PI3K/Akt/mTOR signaling pathway

“…[9] In addition, emerging studies have indicated that SRPX2 plays a critical role in tumorigenesis. [13] However, the role of SRPX2 in prostate cancer has not yet been reported. [13] However, the role of SRPX2 in prostate cancer has not yet been reported.…”