Summary of the papers of Auditing
Research
- Aberrant heterotypic signaling is linked to various pathological
conditions, including
... [Show More] neurodegenerative, cardiovascular, and
autoimmune diseases.
- Heterotypic signaling plays a role in tumorigenesis, often
involving cells in the tumor microenvironment (TME) and cancer
cells.
- Reciprocal communication between fibroblasts and cancer
cells affects cancer cell behavior, but less is known about its
impact on epithelial cells without oncogenic transformation.
- Fibroblasts in close proximity to epithelial cells can undergo
senescence, leading to the secretion of inflammatory cytokines
known as the senescence-associated secretory phenotype
(SASP).
- The SASP can create a permissive environment for cancer cells,
motivating interest in senolytic drugs as a therapeutic strategy.
- Senescent fibroblasts can impact normal epithelial cells,
affecting regeneration and barrier integrity.
- Induction of senescence in fibroblasts results in the secretion of
SASP factors that negatively impact the viability of normal
mammary epithelial cells.
- Activation of oncogenes in mammary epithelial cells protects
them from cell death caused by SASP factors.
- Cell death induced by SASP factors is not apoptosis but
pyroptosis, dependent on the NLRP3 inflammasome, caspase-1,
and gasdermin D.
- Senescent fibroblasts can cause pyroptosis in neighboring
mammary epithelial cells, influencing therapeutic strategies
targeting senescent cells.
Intro Paragraph Summary - ANS-- Normal tissue homeostasis
involves bidirectional communication between different cell
types.
- Reciprocal communication occurs between fibroblasts and
cancer cells, affecting cancer cell behavior.
- The impact of heterotypic interactions on epithelial cell function
without oncogenic transformation is less understood.
- Senescent fibroblasts undergo irreversible cell cycle arrest and
secrete cytokines, known as the senescence-associated
secretory phenotype (SASP).
- Fibroblast-derived SASP factors' role on normal epithelial cells
is poorly understood.
- Conditioned media from senescent fibroblasts (SASP CM)
induces caspase-dependent cell death in normal mammary
epithelial cells.
- SASP CM induces cell death across multiple senescenceinducing stimuli but is mitigated by oncogenic signaling
activation.
- Cell death induced by SASP CM occurs through NLRP3,
caspase-1, and gasdermin D-dependent pyroptosis, not through
extrinsic or intrinsic apoptotic pathways.
- Senescent fibroblasts can cause pyroptosis in neighbouring
mammary epithelial cells, affecting therapeutic strategies
targeting senescent cells [Show Less]