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Semaphorin 5A, an Axon Guidance Molecule, Enhances the Invasion and Metastasis of Human Gastric Cancer through Activation of MMP9

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Pathology & Oncology Research

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.

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Abbreviations

MMPs:

matrix metalloproteinase

ERK:

extracellular signal-regulated kinase

RT-PCR:

reverse-transcription polymerase chain reaction

PBS:

phosphate buffer solution

PVDF:

polyvinylidene difluoride

TBS:

tris-buffer saline

FBS:

fetal bovine serum

Ab:

antibody

ELISA:

enzyme linked immuno sorbent assay

ECM:

extracellular matrix

RGDS:

Arginine-Glycine-Aspartic acid-Serine

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Acknowledgment

The study was supposed by Key Municipal Scientific Project Foundation of Haikou and Provincial Natural Science Foundation of Haikou. We also thank Prof. Shan-ming Hu for kindly revising our paper.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

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Authors and Affiliations

  1. Department of Pathology, The First Affiliated Hospital of Kunming Medical College, Kunming, Yunnan, Peoples Republic of China

    Guoqing Pan, Jianbo Lu & Hongmei Fu

  2. Department of Blood Transfusion, The First Affiliated Hospital of Kunming Medical College, Kunming, Yunnan, Peoples Republic of China

    Xiangling Zhang

  3. Department of Surgery, The First Affiliated Hospital of Kunming Medical College, Kunming, Yunnan, Peoples Republic of China

    Junyu Ren & Wenliang Li

  4. Central Laboratory, Affiliated Hai Kou Hospital, Xiangya Medical College, Central South University, Haikou, Hainan, Peoples Republic of China

    Shufang Zhang

  5. Department of Nephrolog, The First Affiliated Hospital of Kunming Medical College, Kunming, Yunnan, Peoples Republic of China

    Jun Li

  6. Renmin road #43, Haikou, 570208, Hainan, Peoples Republic of China

    Shufang Zhang

Authors
  1. Guoqing Pan
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  2. Xiangling Zhang
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  3. Junyu Ren
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  4. Jianbo Lu
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  5. Wenliang Li
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  6. Hongmei Fu
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  7. Shufang Zhang
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  8. Jun Li
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Corresponding authors

Correspondence to Shufang Zhang or Jun Li.

Additional information

Guoqing Pan Xiangling Zhang and Junyu Ren contributed equally to this work

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Pan, G., Zhang, X., Ren, J. et al. Semaphorin 5A, an Axon Guidance Molecule, Enhances the Invasion and Metastasis of Human Gastric Cancer through Activation of MMP9. Pathol. Oncol. Res. 19, 11–18 (2013). https://doi.org/10.1007/s12253-012-9550-8

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  • DOI: https://doi.org/10.1007/s12253-012-9550-8

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