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Inhibition of Invasion and Metastasis During Specific Amino Acid Restriction Associated with Metastasis Suppressor and Other Gene Changes

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Cancer Metastasis — Related Genes

Part of the book series: Cancer Metastasis — Biology and Treatment ((CMBT,volume 3))

Abstract

Dietary tyrosine (Tyr) and phenylalanine (Phe) restriction dramatically decreases metastasis of a number of implanted murine tumors including melanoma, hepatocarcinoma, lung carcinoma, and leukemia without inducing host toxicity. Herein, we show that Tyr/Phe deprivation in vitro rapidly decreases the intracellularfree Tyr concentration in A375 melanoma cells. The decreased availability of Tyr and Phe to melanoma, prostate, and breast cancer cells in vitro significantly inhibits their invasive ability. MKK4/SEK1 protein expression and/orphosphorylation increased in A375 melanoma and MDA-MB-231 breast cancer cells suggesting an important role for this metastasis suppressor gene in control of invasion during Tyr/Phe deprivation. Additionally, 14 other genes are differentially modulated by Tyr/Phe deprivation. These results suggest that specific intracellular free amino acids regulate the metastatic potential of tumor cells by modulating gene expression and function.

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Authors and Affiliations

  1. Cancer Prevention and Research Center, Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman, WA, 99164-6510

    Gary G. Meadows, Xiaokang Ge, Hui Zhang, Daniel R. Oros & Ya-Min Fu

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  1. Gary G. Meadows
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  2. Xiaokang Ge
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  3. Hui Zhang
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  4. Daniel R. Oros
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  1. Jake Gittlen Cancer Research Institute, The Pennsylvania State University College of Medicine, Pennsylvania, USA

    Danny R. Welch

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© 2002 Kluwer Academic Publishers

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Meadows, G.G., Ge, X., Zhang, H., Oros, D.R., Fu, YM. (2002). Inhibition of Invasion and Metastasis During Specific Amino Acid Restriction Associated with Metastasis Suppressor and Other Gene Changes. In: Welch, D.R. (eds) Cancer Metastasis — Related Genes. Cancer Metastasis — Biology and Treatment, vol 3. Springer, Dordrecht. https://doi.org/10.1007/0-306-47821-8_10

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  • DOI: https://doi.org/10.1007/0-306-47821-8_10

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-1-4020-0522-0

  • Online ISBN: 978-0-306-47821-5

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