Methionine deprivation suppresses triple-negative breast cancer metastasis in vitro and in vivo

Hyein Jeon, Jae Hwan Kim, Eunjung Lee, Young Jin Jang, Joe Eun Son, Jung Yeon Kwon, Tae gyu Lim, Sunghoon Kim, Jung Han Yoon Park, Jong Eun Kim, Ki Won Lee

Research output: Contribution to journalArticlepeer-review

72 Citations (Scopus)

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 methioninedeprived 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.

Original languageEnglish
Pages (from-to)67223-67234
Number of pages12
JournalOncotarget
Volume7
Issue number41
DOIs
Publication statusPublished - 2016

All Science Journal Classification (ASJC) codes

  • Oncology

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