title: APRIL induces tumorigenesis and metastasis of colorectal cancer cells via activation of the PI3K/Akt pathway.
abstract: A proliferation-inducing ligand (APRIL) is highly expressed in colorectal cancer (CRC) tissues and cell lines. However, the biological functions and precise signals elicited by APRIL in CRC have not been fully understood. Here, we used small interfering RNA to selectively deplete APRIL and to determine its tumorigenic effects in a CRC cell line SW480 both in vitro and in vivo. Knockdown of APRIL in SW480 cells was associated with modulation of cell proliferation as well as reduction of cell migration and invasion in vitro. Moreover APRIL-knockdown SW480 cells displayed markedly inhibited tumor growth and decreased metastasis to the liver in immunodeficient mice upon subcutaneous injection. Importantly, we observed that downregulation of APRIL in SW480 cells resulted in greatly decreased activity of phosphoinositide 3-kinase (PI3K)/Akt pathway. In addition, we observed that recombinant human APRIL mediated activation of the PI3K/Akt pathway in CRC cells resulting in induced expression of important cell cycle proteins and matrix metalloproteinases in a PI3K/Akt dependent manner. This was concurrent with marked cell growth viability as well as increased cell migration and invasion. Together, these compelling data suggest that APRIL-induced tumorigenesis and metastasis of CRC cells may be accomplished through activation of the PI3K/Akt pathway. These findings may lead to a better understanding of the biological effects of APRIL and may provide clues for identifying novel therapeutic and preventive molecular markers for CRC.
authors: Department of Clinical Laboratory Center, Affiliated Hospital of Nantong University, School of Public Health, Nantong University, Nantong, Jiangsu, People's Republic of China.
authors: Guihua
authors: G
authors: Wang
authors: Feng
authors: F
authors: Wang
authors: Weifeng
authors: W
authors: Ding
authors: Jingchun
authors: J
authors: Wang
authors: Rongrong
authors: R
authors: Jing
authors: Haiquan
authors: H
authors: Li
authors: Xudong
authors: X
authors: Wang
authors: Yueguo
authors: Y
authors: Wang
authors: Shaoqing
authors: S
authors: Ju
authors: Huimin
authors: H
authors: Wang
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000503:physiopathology*; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D034741:RNA, Small Interfering; C114631:TNFSF13 protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D019869:Phosphatidylinositol 3-Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
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