The interplay between autophagy, p16 INK4a , and senescence in tumor cells: a systematic review.

In 30 seconds

This systematic review examined how autophagy and p16INK4a interact with cellular senescence in tumor cells. A search of three databases identified 10 eligible studies published between January 2000 and April 2025. Across the evidence, autophagy sometimes increased p16INK4a and senescence-associated β-gal activity, promoting stable growth arrest, but under stress it could also support tumor-cell survival despite senescence signals. p16INK4a appeared to act both upstream and downstream in this relationship. Heterogeneity among studies limited direct comparisons.

Key findings

• The systematic review included 10 eligible studies identified through searches of PubMed, Web of Science, and Scopus.
• In some models, autophagy increased p16INK4a and senescence-associated β-gal activity, leading to stable growth arrest.
• Under stress conditions, autophagy could support tumor-cell survival despite senescence signals.
• p16INK4a was reported to modulate autophagic flux and to act as an effector of autophagy-induced senescence.

Why it matters

The review highlights that autophagy may accompany either tumor-cell growth arrest or survival, depending on context, and that p16INK4a participates in both directions of this relationship. This complexity matters when interpreting these pathways as potential therapeutic targets: their effects may not be uniform across tumor models, and the current evidence does not establish a consistent intervention strategy.

What to keep in mind

Heterogeneity among the included studies limited direct comparisons.