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Under hypoxia conditions contactin-1 regulates the migration of Mkn45 cells through the RhoA pathway

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Abstract

Recent studies have suggested that contactin-1 has a key role in cancer cell proliferation and migration, however the detailed mechanism of this process is still unclear. Here, human gastric cancer cell line MKN45 was employed. It was found that under hypoxia conditions contactin-1 mRNA and protein levels were both up-regulated by HIF-1α expression. Furthermore, although hypoxia increased the migration rate of MKN45 cells, contactin-1 (CNTN1) shRNA reversed this process. Meanwhile, RhoA V14 and RhoA V14 N19 mutation constructs were employed, and it was found that constitutively active form of RhoA reversed the cell migration suppression induced by contactin-1 knockdown, while dominant-negative form of RhoA blocked hypoxia induced hypermigration. Apart from this, contactin-1 displayed the ability to phosphorylate the RhoA activator p115 RhoGEF. Thus, under hypoxia conditions, elevated HIF-1α seems to up-regulate contactin-1 expression and by this activate RhoA and facilitate migration of cancer cells.

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Authors and Affiliations

  1. Xishan out-patient Department, The 309th Hospital of PLA, Beijing, 100091, P.R. China

    G. Yang

  2. Department of Gastroenterology, the 309th Hospital of PLA, Beijing, 100091, P.R. China

    J. -G. Song

  3. Department of Oncology, Kunming General Hospital of Chengdu military force, Kunming, 650032, China

    Y. Li

  4. Department of Obstetrics and Gynecology in Nanfang Hospital, Southern Medical University, Guang zhou, 510515, China

    S. -P. Gong

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  1. G. Yang
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  2. J. -G. Song
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  3. Y. Li
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  4. S. -P. Gong
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Correspondence to S. -P. Gong.

Additional information

Published in Russian in Molekulyarnaya Biologiya, 2015, Vol. 49, No. 1, pp. 129–137.

The article is published in the original.

The authors contributed equally to the work.

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Yang, G., Song, J.G., Li, Y. et al. Under hypoxia conditions contactin-1 regulates the migration of Mkn45 cells through the RhoA pathway. Mol Biol 49, 112–119 (2015). https://doi.org/10.1134/S0026893315010185

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  • DOI: https://doi.org/10.1134/S0026893315010185

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