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 non-oxidative pentose pathway for purine synthesis. Silencing expression of fructose-1,6-bisphosphatases (FBPs) 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.
Methotrexate
(MTX), a folate antagonist drug, has been widely used
for treating various cancers. Since high-dose MTX treatment can cause
unwanted serious side effects, tracking the blood concentration of
MTX is essential for safe medication. However, available methods are
often complex, time-consuming, and expensive. In this study, a highly
selective DNA aptamer was selected for recognizing MTX based on a
capture–systematic evolution of ligands by an exponential enrichment
(C-SELEX) approach. Taking advantage of our selected MTX aptamer,
we further unveil a novel structure-switching fluorescent sensor for
the specific and rapid monitoring of MTX with good analytical performances
(i.e., a linear detection range of 0.1–2 μM with a low
detection limit (LOD) of 0.03 μM in buffer and a linear detection
range of 0.5–10 μM with an LOD of 0.18 μM in 50%
serum). Compared with conventional methods, this assay has great potential
for detecting the blood concentration of MTX in clinical use. By coupling
with other sensory techniques, our presented aptamer will potentially
inspire the development of various sensors toward the monitoring of
MTX.
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