{
  "id": 18113093,
  "title": "Targeting tankyrase scaffolding in the β-catenin destruction complex by PROTAC overcomes the limitation of catalytic inhibitors in colorectal cancer",
  "url": "https://urgent.news/2026/11/04/targeting-tankyrase-scaffolding-in-the-catenin-destruction-complex-by",
  "topic": "health",
  "section": "Health & Medicine",
  "published": "2026-11-04T00:00:00.000Z",
  "source": {
    "name": "eLife",
    "slug": "elife",
    "url": "https://elifesciences.org/articles/109052"
  },
  "original_language": "en",
  "account": "Aberrant WNT/β-catenin signaling is a key driver of tumor growth and spread in cancer. While inhibiting tankyrase (TNKS), an enzyme involved in this pathway, can block the degradation of AXIN and stabilize the β-catenin destruction complex (DC), TNKS inhibitors have shown limited success in treating colorectal cancer (CRC). The researchers discovered that inducing AXIN puncta formation poses a major obstacle to achieving effective therapy. When TNKS is inhibited, it prevents its turnover, leading to its accumulation within the DC. Here, TNKS' scaffolding function induces the formation of AXIN puncta, which rigidifies the DC and hinders β-catenin turnover. To overcome this limitation, the researchers chemically degraded TNKS, which stabilized AXIN without puncta formation. This approach provided deeper suppression of the WNT/β-catenin pathway activity and reduced the proliferation of CRC cells with dysfunctional APC mutations. The findings explain why TNKS inhibitors have not been successful in treating WNT/β-catenin-driven CRC and suggest that targeting TNKS degradation could be a promising strategy for treating this type of cancer.",
  "summary": "Aberrant WNT/β-catenin signaling drives tumorigenesis and metastasis in cancer. Although enzymatic inhibitors of tankyrase (TNKS) effectively block AXIN degradation and stabilize the β-catenin destruction complex (DC), they have demonstrated limited efficacy in various colorectal cancer (CRC) models. Here, we demonstrate that, unexpectedly, the induction of AXIN puncta represents a major barrier…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}