UMMS Affiliation

Program in Molecular Medicine

Date

8-26-2016

Document Type

Article

Disciplines

Cancer Biology

Abstract

Nutrient deprivation strategies have been proposed as an adjuvant therapy for cancer cells due to their increased metabolic demand. We examined the specific inhibitory effects of amino acid deprivation on the metastatic phenotypes of the human triple-negative breast cancer (TNBC) cell lines MDA-MB-231 and Hs 578T, as well as the orthotopic 4T1 mouse TNBC tumor model. Among the 10 essential amino acids tested, methionine deprivation elicited the strongest inhibitory effects on the migration and invasion of these cancer cells. Methionine deprivation reduced the phosphorylation of focal adhesion kinase, as well as the activity and mRNA expression of matrix metalloproteinases MMP-2 and MMP-9, two major markers of metastasis, while increasing the mRNA expression of tissue inhibitor of metalloproteinase 1 in MDA-MB-231 cells. Furthermore, methionine restriction downregulated the metastasis-related factor urokinase plasminogen activatior and upregulated plasminogen activator inhibitor 1 mRNA expression. Animals on the methionine-deprived diet showed lower lung metastasis rates compared to mice on the control diet. Taken together, these results suggest that methionine restriction could provide a potential nutritional strategy for more effective cancer therapy.

Rights and Permissions

Citation: Oncotarget. 2016 Oct 11;7(41):67223-67234. doi: 10.18632/oncotarget.11615. Link to article on publisher's site

DOI of Published Version

10.18632/oncotarget.11615

Related Resources

Link to Article in PubMed

Keywords

cancer therapy metastasis, methionine, triple-negative breast cancer

Journal Title

Oncotarget

PubMed ID

27579534

Creative Commons License

Creative Commons Attribution 3.0 License
This work is licensed under a Creative Commons Attribution 3.0 License.

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