Gain of Glucose-Independent Growth upon Metastasis of Breast Cancer Cells to the Brain
Autor: | Lewis C. Cantley, Sun Jin Kim, Guang Gao, Jason W. Locasale, Yan Wang, Zhang Weihua, Tamar Melman, Lei Huo, Xuefeng Wu, John M. Asara, Jinyu Chen, James M. Briggs, Lei Xu, Fei Su, Ho Jeong Lee, Junqing He, Lakshmi Reddy Bollu, Isaiah J. Fidler, Xiaojing Liu |
---|---|
Rok vydání: | 2015 |
Předmět: |
Cancer Research
medicine.medical_specialty Cell Survival Breast Neoplasms Biology Mass Spectrometry Article Metastasis Mice chemistry.chemical_compound Breast cancer Cell Line Tumor Internal medicine medicine Animals Humans Gene silencing Gene Silencing Amino Acids RNA Small Interfering Cell Proliferation Mice Inbred BALB C Glycogen Brain Neoplasms Brain Cancer medicine.disease Fructose-Bisphosphatase Oxygen Glutamine Glucose Endocrinology Oncology chemistry Cancer cell Cancer research Female Glycolysis Brain metastasis |
Zdroj: | Cancer Research. 75:554-565 |
ISSN: | 1538-7445 0008-5472 |
Popis: | Breast cancer brain metastasis is resistant to therapy and a particularly poor prognostic feature in patient survival. Altered metabolism is a common feature of cancer cells, but little is known as to what metabolic changes benefit breast cancer brain metastases. We found that brain metastatic breast cancer cells evolved the ability to survive and proliferate independent of glucose due to enhanced gluconeogenesis and oxidations of glutamine and branched chain amino acids, which together sustain the nonoxidative pentose pathway for purine synthesis. Silencing expression of fructose-1,6-bisphosphatases (FBP) in brain metastatic cells reduced their viability and improved the survival of metastasis-bearing immunocompetent hosts. Clinically, we showed that brain metastases from human breast cancer patients expressed higher levels of FBP and glycogen than the corresponding primary tumors. Together, our findings identify a critical metabolic condition required to sustain brain metastasis and suggest that targeting gluconeogenesis may help eradicate this deadly feature in advanced breast cancer patients. Cancer Res; 75(3); 554–65. ©2014 AACR. |
Databáze: | OpenAIRE |
Externí odkaz: |