colorectal-cancer

Autophagy protein p62 plays a dual role in colorectal cancer—suppressing inflammation early but driving tumorigenesis when it accumulates.

p62 has context-dependent dual roles in CRC: in early inflammation, p62 suppresses tumors by clearing inflammasomes, activating NRF2, and downregulating inflammatory cytokines. But sustained inflammation causes p62 accumulation, reinforcing NRF2, NF-κB, and mTORC1 activation through positive…

Dan Manning

Dan Manning

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Autophagy protein p62 plays a dual role in colorectal cancer—suppressing inflammation early but driving tumorigenesis when it accumulates.

Autophagy protein p62 plays a dual role in colorectal cancer—suppressing inflammation early but driving tumorigenesis when it accumulates.

p62 has context-dependent dual roles in CRC: in early inflammation, p62 suppresses tumors by clearing inflammasomes, activating NRF2, and downregulating inflammatory cytokines. But sustained inflammation causes p62 accumulation, reinforcing NRF2, NF-κB, and mTORC1 activation through positive feedback loops, driving tumorigenesis. Excess p62 also impairs DNA double-strand break repair.

Key Findings

  • p62 has tumor-suppressive functions in early CRC inflammation
  • Sustained inflammation causes p62 accumulation with oncogenic consequences
  • p62 accumulation reinforces NRF2, NF-κB, mTORC1 activation
  • Excessive p62 impairs DNA double-strand break repair
  • Enhancing autophagic p62 clearance could prevent inflammation-associated CRC

Implications

Promoting autophagic clearance of p62 is a potential strategy to prevent CRC development in patients with inflammatory bowel disease or chronic colitis.

Caveats

Review article; abstract-only. Dual role context-dependency complicates therapeutic targeting. Preclinical evidence; clinical translation unclear.

Source: Frontiers in immunology — 2026-01-01

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