0000000000179114
AUTHOR
Elisa Lipari
MYC-driven epigenetic reprogramming favors the onset of tumorigensis by inducing a stem cell-like state
AbstractBreast cancer consists of highly heterogeneous tumors, whose cell of origin and driver oncogenes resulted difficult to be uniquely defined. Here we report that MYC acts as tumor reprogramming factor in mammary epithelial cells by inducing an alternative epigenetic program, which triggers loss of cell identity and activation of oncogenic pathways. Over-expression of MYC induces transcriptional repression of lineage-specifying transcription factors, causing decommissioning of luminal-specific enhancers. MYC-driven dedifferentiation supports the onset of a stem cell-like state by inducing the activation of de novo enhancers, which drive the transcriptional activation of oncogenic pathw…
DEVELOPMENT AND QUALIFICATION OF BIOANALYTICAL METHODS FOR DEAMIDATED IFNβ-1a AND INVESTIGATION ABOUT THE MECHANISM OF ACTION
Interferon beta-1a (IFNβ-1a) is a recombinant IFNβ with the tradename Rebif involved in several biological activities. Recently, it has been reported that artificial deamidation of IFNb-1a increases its biological response. Given the therapeutical potential, an investigation on the deamidated variant has been carried out via different approaches to discover the mechanism underlying this biological effect. The antiviral and immunomodulatory activity of deamidated cytokine was assessed using two precise and accurate cell-based assays. As expected, deamidated IFNβ-1a showed an increase in the biological response and its canonical pathway and receptor binding affinity were thorough analysed. De…
IL4 Primes the Dynamics of Breast Cancer Progression via DUSP4 Inhibition
Abstract The tumor microenvironment supplies proinflammatory cytokines favoring a permissive milieu for cancer cell growth and invasive behavior. Here we show how breast cancer progression is facilitated by IL4 secreted by adipose tissue and estrogen receptor–positive and triple-negative breast cancer cell types. Blocking autocrine and paracrine IL4 signaling with the IL4Rα antagonist IL4DM compromised breast cancer cell proliferation, invasion, and tumor growth by downregulating MAPK pathway activity. IL4DM reduced numbers of CD44+/CD24− cancer stem-like cells and elevated expression of the dual specificity phosphatase DUSP4 by inhibiting NF-κB. Enforced expression of DUSP4 drove conversio…
MYC-driven epigenetic reprogramming favors the onset of tumorigenesis by inducing a stem cell-like state
Breast cancer consists of highly heterogeneous tumors, whose cell of origin and driver oncogenes are difficult to be uniquely defined. Here we report that MYC acts as tumor reprogramming factor in mammary epithelial cells by inducing an alternative epigenetic program, which triggers loss of cell identity and activation of oncogenic pathways. Overexpression of MYC induces transcriptional repression of lineage-specifying transcription factors, causing decommissioning of luminal-specific enhancers. MYC-driven dedifferentiation supports the onset of a stem cell-like state by inducing the activation of de novo enhancers, which drive the transcriptional activation of oncogenic pathways. Furthermo…