Evolutionary conserved reciprocal senescence and tumor suppressor signals limit lifetime cancer
Liu, L.; Davis, S.; Yusuff, S.; Strange, A.; Zhuang, Y.; Vaddi, P.; Flaherty, K.; Jara, K.; Kramer, J.; Archer, C.; Lee, S.; Gao, B.; van Bokhoven, A.; Wang, W.; Pine, S. R.; Nakamura, T.; Sabaawy, H. E.
Show abstract
Cellular senescence features a durable exit from the cell cycle triggered by stress or carcinogens. The INK4 locus is inactivated in various cancers, yet in senescence, p16Ink4a is activated. Whether senescence is tumor-suppressing or -promoting remains a conundrum. We discovered an evolutionally-conserved Vertebrata INK4-homolog. This ink4ab triggers senescence upon oxidative- and/or carcinogenic-stress. Adult Ink4ab-deficient animals failed to activate senescence and developed spontaneous cancers. Combined Ink4ab and Tp53 deficiency revealed a reciprocal senescence and apoptosis regulation, controlling tumorigenesis, including retinoblastoma. INK4-hematopoietic-deficient mice exhibited p19Arf-dependent enhanced senescence-like phenotypes, uncontrolled cell proliferation, defective stem cell differentiation, and splenomegaly, with single-splenocytes spatially-enriched in senescence-associated secretory profiles. Our studies reveal the evolutionary origin of paradigms co-regulating senescence and tumor suppression and offer strategies to exploit these reciprocal pathways for cancer prevention and therapy.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- The intensities of canonical senescence biomarkers integrate the duration of cell-cycle withdrawal 96%
- Digital telomere measurement by long-read sequencing distinguishes healthy aging from disease 95%
- Single-cell RNA sequencing reveals distinct senotypes and a quiescence-senescence continuum at the transcriptome level following chemotherapy 95%
Similar papers in this journal
Similar papers in this journal
- Single-PanIN-seq Unveils that ARID1A Deficiency Promotes Pancreatic Tumorigenesis by Attenuating KRAS Induced Senescence 96%
- Activity-dependent synapse elimination requires caspase-3 activation 94%
- Revisiting the Hayflick Limit: Insights from an Integrated Analysis of Changing Transcripts, Proteins, Metabolites and Chromatin 94%
Similar papers in this journal
- Abolishing the prelamin A ZMPSTE24 cleavage site leads to progeroid phenotypes with near-normal longevity in mice 95%
- Ki-67 promotes sequential stages of tumourigenesis by enabling cellular plasticity 95%
- T Lymphocyte-Specific Deletion of SHP1 and SHP2 Promotes Activation-Induced Cell Death of CD4+ T Cells and Impairs Antitumor Response 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.