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Reciprocal regulation of MelCAM and AKT in human melanoma

Oncogene volume 22, pages 6891–6899 (2003)Cite this article

Abstract

Alteration in the expression of invasion/metastasis-related melanoma cell adhesion molecule (MelCAM) is strongly associated with the acquisition of malignancy by human melanoma. However, little is known about the molecular and biochemical mechanisms that regulate the expression and function of MelCAM, or its downstream signaling transduction. In this study, we show that there is a reciprocal regulation loop between AKT and MelCAM. Pharmacological inhibition of AKT in human melanoma cell lines substantially reduced the expression of MelCAM. Overexpression of constitutively active AKT upregulated the levels of MelCAM in melanoma cell lines, whereas expression of a dominant-negative PI-3 kinase downregulated MelCAM. On the other hand, overexpression of MelCAM activated endogenous AKT and inhibited proapoptotic protein BAD in melanoma cells, leading to increased survival under stress conditions. Constitutive activation of AKT was observed in most melanoma cell lines and tumor samples of different progression stages. These data link AKT activation with MelCAM expression, and implicate that intervention of MelCAM-AKT signaling axis in melanoma is a potential therapeutical approach.

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Acknowledgements

We thank all members of Herlyn lab for technical and intellectual support. This work was supported by the National Institutes of Health Grants CA-25874, CA-76674, CA-47159, CA-80999 and CA-10815.

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Authors and Affiliations

  1. The Wistar Institute, 3601 Spruce Street, Philadelphia, 19104, PA, USA

    Gang Li, Jiri Kalabis, Friedegund Meier, Thomas Bogenrieder & Meenhard Herlyn

  2. Department of Pathology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, 19104, PA, USA

    Xiaowei Xu

  3. Department of Dermatology, Kobe University School of Medicine, Kobe, 650-0017, Japan

    Masahiro Oka

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  1. Gang Li
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Correspondence to Meenhard Herlyn.

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Li, G., Kalabis, J., Xu, X. et al. Reciprocal regulation of MelCAM and AKT in human melanoma. Oncogene 22, 6891–6899 (2003). https://doi.org/10.1038/sj.onc.1206819

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