title: Semaphorin 5A, an axon guidance molecule, enhances the invasion and metastasis of human gastric cancer through activation of MMP9.
abstract: Semaphorin 5A, a member of semaphorin family, was originally identified as axonal guidance factor functioning during neuronal development. Previously, we showed that the expression of semaphorin 5A might contribute to the metastasis of gastric cancer. However, its functional roles and mechanism(s) in invasion and metastasis of gastric cancer remain unclear. By using human gastric caner cell lines Parental SGC7901, SGC7901-siScrambled and SGC7901-siSema 5A, we found that semaphorin 5A significantly promoted the invasive and metastatic abilities of gastric cancer cell in vitro. Semaphorin 5A increased the expression of MMP9 by activating phosphorylated ErK1/2 in gastric cancer cell. Furthermore, MEK inhibitor PD98059 and MMP9 antibody (Ab) significantly inhibited in vitro invasive and metastatic abilities induced by semaphorin 5A. Taken together, the present work revealed a novel function of semaphorin 5A that the existence of semaphorin 5A could promote invasion and metastasis of gastric cancer by regulating MMP9 expression, at least partially, via the MEK/ERKs signal transduction pathway. Semaphorin 5A and its regulated molecules could be the potential targets for cancer therapy.
authors: Department of Pathology, The First Affiliated Hospital of Kunming Medical College, Kunming, Yunnan, Peoples Republic of China.
authors: Guoqing
authors: G
authors: Pan
authors: Xiangling
authors: X
authors: Zhang
authors: Junyu
authors: J
authors: Ren
authors: Jianbo
authors: J
authors: Lu
authors: Wenliang
authors: W
authors: Li
authors: Hongmei
authors: H
authors: Fu
authors: Shufang
authors: S
authors: Zhang
authors: Jun
authors: J
authors: Li
mesh_terms: D000704:Analysis of Variance; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D016023:Integrins / Q000378:metabolism; D020935:MAP Kinase Signaling System; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000378:metabolism*; D039961:Semaphorins; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: D005419:Flavonoids; D016023:Integrins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C491228:SEMA5A protein, human; D039961:Semaphorins; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one