5 research outputs found
Stress-Induced Epinephrine Enhances Lactate Dehydrogenase A and Promotes Breast Cancer Stem-Like Cells
Chronic stress triggers activation of the sympathetic nervous system and drives malignancy. Using an immunodeficient murine system, we showed that chronic stress–induced epinephrine promoted breast cancer stem-like properties via lactate dehydrogenase A–dependent (LDHA-dependent) metabolic rewiring. Chronic stress–induced epinephrine activated LDHA to generate lactate, and the adjusted pH directed USP28-mediated deubiquitination and stabilization of MYC. The SLUG promoter was then activated by MYC, which promoted development of breast cancer stem-like traits. Using a drug screen that targeted LDHA, we found that a chronic stress–induced cancer stem-like phenotype could be reversed by vitamin C. These findings demonstrated the critical importance of psychological factors in promoting stem-like properties in breast cancer cells. Thus, the LDHA-lowering agent vitamin C can be a potential approach for combating stress-associated breast cancer
Unconventional Charge-density-wave Order in a Dilute d-band Semiconductor
Electron-lattice coupling effects in low dimensional materials give rise to
charge density wave (CDW) order and phase transitions. These phenomena are
critical ingredients for superconductivity and predominantly occur in metallic
model systems such as doped cuprates, transition metal dichalcogenides, and
more recently, in Kagome lattice materials. However, CDW in semiconducting
systems, specifically at the limit of low carrier concentration region, is
uncommon. Here, we combine electrical transport, synchrotron X-ray diffraction
and optical spectroscopy to discover CDW order in a quasi-one-dimensional (1D),
dilute d-band semiconductor, BaTiS3, which suggests the existence of strong
electron-phonon coupling. The CDW state further undergoes an unusual transition
featuring a sharp increase in carrier mobility. Our work establishes BaTiS3 as
a unique platform to study the CDW physics in the dilute filling limit to
explore novel electronic phases
Stress-induced epinephrine enhances lactate dehydrogenase A and promotes breast cancer stem-like cells
Chronic stress triggers activation of the sympathetic nervous system and drives malignancy. Using an immunodeficient murine system, we showed that chronic stress-induced epinephrine promoted breast cancer stem-like properties via lactate dehydrogenase A-dependent (LDHA-dependent) metabolic rewiring. Chronic stress-induced epinephrine activated LDHA to generate lactate, and the adjusted pH directed USP28-mediated deubiquitination and stabilization of MYC. The SLUG promoter was then activated by MYC, which promoted development of breast cancer stem-like traits. Using a drug screen that targeted LDHA, we found that a chronic stress-induced cancer stem-like phenotype could be reversed by vitamin C. These findings demonstrated the critical importance of psychological factors in promoting stem-like properties in breast cancer cells. Thus, the LDHA-lowering agent vitamin C can be a potential approach for combating stress-associated breast cancer
The Molecular Taxonomy of Primary Prostate Cancer
There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defectsclose