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ARHGEF39 promotes gastric cancer cell proliferation and migration via Akt signaling pathway

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Abstract

Dbl-family guanine nucleotide exchange factors (GEFs) can activate RhoGTPases by facilitating the exchange of GDP for GTP, the aberrant expression of which has been implicated in tumorigenicity and metastasis of human cancers. ARHGEF39, as a member of Dbl-family GEFs, was reported to be a potential oncogene in human hepatocellular carcinoma previously. However, the role of ARHGEF39 in gastric cancer (GC) remains unclear so far. In the current study, we demonstrated that ARHGEF39 expression was significantly upregulated in GC tissues compared with paired adjacent normal tissues by quantitative real-time PCR analysis. Functional analyses revealed that ARHGEF39 overexpression could promote proliferation, colony formation, and migration of GC cells in vitro, whereas ARHGEF39 knockdown markedly suppressed these phenotypes. Moreover, ARHGEF39 enhanced tumorigenicity and lung metastasis potential of GC cells in nude mice model. Mechanistically, we found that overexpressed ARHGEF39 significantly increased the phosphorylation level of Akt (p-Akt), and its effect on cell proliferation was attenuated by PI3K inhibitor LY294002. Thus, our findings suggest that ARHGEF39 may contribute to cell proliferation and migration in GC via a possible mechanism involving Akt signaling.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 81302490).

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Author notes

  1. Haixiao Wang and Miaomiao Li contributed equally to this study.

Authors and Affiliations

  1. Department of General Surgery, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, 223300, Jiangsu, China

    Haixiao Wang, Yan Qian & Guoquan Tao

  2. Department of Gastroenterology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, 223300, Jiangsu, China

    Miaomiao Li

  3. Department of Psychiatry, Huai’an Third People’s Hospital, Huai’an, 223001, Jiangsu, China

    Xiaobao Tao

  4. Department of Neurology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, 223300, Jiangsu, China

    Linfang Chen

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  1. Haixiao Wang
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  2. Miaomiao Li
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  3. Xiaobao Tao
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  4. Yan Qian
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Correspondence to Linfang Chen or Guoquan Tao.

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Wang, H., Li, M., Tao, X. et al. ARHGEF39 promotes gastric cancer cell proliferation and migration via Akt signaling pathway. Mol Cell Biochem 440, 33–42 (2018). https://doi.org/10.1007/s11010-017-3153-3

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  • DOI: https://doi.org/10.1007/s11010-017-3153-3

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