Methionine deprivation suppresses triple-negative breast cancer metastasis in vitro and in vivo
Authors
Jeon, HyeinKim, Jae Hwan
Lee, Eunjung
Jang, Young Jin
Son, Joe Eun
Kwon, Jung Yeon
Lim, Tae-Gyu
Kim, Sunghoon
Park, Jung Han Yoon
Kim, Jong-Eun
Lee, Ki Won
UMass Chan Affiliations
Program in Molecular MedicineDocument Type
Journal ArticlePublication Date
2016-08-26
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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.Source
Oncotarget. 2016 Oct 11;7(41):67223-67234. doi: 10.18632/oncotarget.11615. Link to article on publisher's siteDOI
10.18632/oncotarget.11615Permanent Link to this Item
http://hdl.handle.net/20.500.14038/40123PubMed ID
27579534Related Resources
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10.18632/oncotarget.11615
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