An unscheduled switch to endocycles induces a reversible senescent arrest that impairs growth of theDrosophilawing disc

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 14, 2024

Summary A programmed developmental switch to G / S endocycles results in tissue growth through an increase cell size. Unscheduled, induced endocycling cells (iECs) promote wound healing but also contribute cancer. Much remains unknown, however, about how these iECs affect growth. Using the D. melanogaster wing disc as model, we find that populations of initially size then subsequently undergo a heterogenous arrest causes severe undergrowth. acquired DNA damage and activated Jun N-terminal kinase (JNK) pathway, but, unlike other stressed cells, were apoptosis-resistant not eliminated from epithelium. Instead, entered JNK-dependent reversible senescent-like arrest. Senescent promoted division diploid neighbors, this compensatory proliferation did rescue Our study has uncovered unique attributes their effects on have important implications for understanding roles

Язык: Английский

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Too big not to fail: emerging evidence for size‐induced senescence

FEBS Journal, Год журнала: 2023, Номер 291(11), С. 2291 - 2305

Опубликована: Ноя. 20, 2023

Cellular senescence refers to a permanent and stable state of cell cycle exit. This process plays an important role in many cellular functions, including tumor suppression. It was first noted that is associated with increased size the early 1960s; however, how this contributes exit poorly understood until recently. In review, we discuss new findings identify as not only consequence but also cause We highlight recent insights into alters normal physiology creates homeostatic imbalances contribute induction. Finally, focus on potential clinical implications these context arrest‐causing cancer therapeutics speculate changes may impact outcomes patients treated drugs.

Язык: Английский

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Targeting metabolism to influence cellular senescence a promising anti-cancer therapeutic strategy

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 177, С. 116962 - 116962

Опубликована: Июнь 26, 2024

Metabolic disorders are considered the hallmarks of cancer and metabolic reprogramming is emerging as a new strategy for treatment. Exogenous endogenous stressors can induce cellular senescence; interactions between senescence systemic metabolism dynamic. Cellular disrupts homeostasis in various tissues, which further promotes senescence, creating vicious cycle facilitating tumor occurrence, recurrence, altered outcomes anticancer treatments. Therefore, regulation related secretory phenotypes breakthrough therapy; moreover, proteins involved associated pathways prospective therapeutic targets. Although studies on association tumors have emerged recent years, elucidation this complex correlation required comprehensive knowledge. In paper, we review research progress cell aging metabolism, focusing strategies targeting to modulate relevant context anti-tumor therapy. Finally, discuss significance improving specificity safety anti-senescence drugs, potential challenge

Язык: Английский

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A hybrid epithelial-mesenchymal transition program enables basal epithelial cells to bypass stress-induced stasis and contributes to a metaplastic breast cancer progenitor state

Breast Cancer Research, Год журнала: 2024, Номер 26(1)

Опубликована: Дек. 18, 2024

Язык: Английский

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Too big not to fail: Different paths lead to senescence of enlarged cells

Molecular Cell, Год журнала: 2023, Номер 83(22), С. 3946 - 3947

Опубликована: Ноя. 1, 2023

Язык: Английский

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