Sulfatase-2 promotes the growth and metastasis of colorectal cancer by activating Akt and Erk1/2 pathways.
The molecular mechanisms underlying the growth and metastasis of colorectal cancer (CRC) remain largely unknown. Sulfatase-2 (SULF2) was found to play critical roles in human cancers. Recent study reported that SULF1/2 overexpression resulted in increased viability and proliferation, and augmented cell migration in CRC cells. However, the expression of SULF2 and its underlying molecular mechanisms in CRC remain unknown. In this study, we found that the expressions of SULF2 in CRC tissues and cell lines were significantly increased compared to control groups. Increased expression of SULF2 was associated with malignant clinical features and poor prognosis of CRC patients. Loss of SULF2 significantly prohibited the proliferation, cell cycle progression, migration and invasion of HT29 cells, while restoration of SULF2 significantly promoted these cellular functions of SW480 cells. In vivo tumorigenicity and liver metastasis assays confirmed that SULF2 knockdown significantly reduced the growth and metastatic abilities of HT29 cells in nude mice. Furthermore, SULF2 knockdown reduced the levels of p-Akt and p-Erk1/2 in HT29 cells, while SULF2 overexpression showed opposite effects on the expressions of these proteins in SW480 cells. In all, SULF2 promotes the growth and metastasis of CRC probably by activating Akt and Erk1/2 pathways. SULF2 potentially serves as a promising biomarker and therapeutic target in CRC.
Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun 130033, China.
Youmao
Y
Tao
Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun 130033, China.
Tao
T
Han
Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun 130033, China.
Tao
T
Zhang
Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun 130033, China. Electronic address: scx_cjuh@163.com.
Caixia
C
Sun
D000368:Aged; D000818:Animals; D018938:Caco-2 Cells; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D055785:Gene Knockdown Techniques / Q000379:methods; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000493:pharmacokinetics*; D015398:Signal Transduction / Q000502:physiology; D013429:Sulfatases; D015238:Sulfotransferases / Q000378:metabolism*
D051057:Proto-Oncogene Proteins c-akt; D015238:Sulfotransferases; C470792:SULF2 protein, human; D013429:Sulfatases
Cancer growth; Cancer metastasis; Colorectal cancer; Signaling pathway; Sulfatase-2