{
  "id": 5484513,
  "title": "A CD109-SMURF2 Axis Diverts EGFR from Degradation to Sustain Oncogenic Signaling and Promote Squamous Cell Carcinoma Invasion and Stemness",
  "url": "https://urgent.news/2026/09/03/a-cd109-smurf2-axis-diverts-egfr-from-degradation-to-sustain",
  "topic": "world",
  "section": "World",
  "published": "2026-09-03T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.02.748398v1?rss=1"
  },
  "original_language": "en",
  "account": "Squamous cell carcinoma (SCC), particularly recurrent or metastatic disease, poses significant treatment challenges. EGFR signaling, a known driver of SCC, remains incompletely understood in terms of its regulatory mechanisms. CD109, a GPI-anchored glycoprotein often found at elevated levels in SCC, has been linked to EGFR signaling, yet its precise role remains unclear. This study reveals that CD109 is not only overexpressed in head and neck SCC (HNSCC) according to the TCGA PanCancer Atlas but also correlates strongly with reduced disease-free survival. Comprehensive transcriptomic and proteomic analyses from the TCGA PanCancer Atlas and LinkedOmics, respectively, show robust positive correlations between CD109, EGFR, and SMURF2. These associations were confirmed through immunohistochemistry in HNSCC patient samples.\n\nFunctionally, CD109 overexpression disrupts EGFR degradation, reduces EGFR pY1045 phosphorylation, and boosts EGFR pY1068 phosphorylation, leading to heightened STAT3, AKT, and ERK signaling. SMURF2 emerges as a crucial mediator of these effects, with CD109 facilitating EGFR-SMURF2 complex formation. Gain- and loss-of-function studies in SCC cells demonstrate that SMURF2 stabilizes EGFR by diminishing its interaction with the ubiquitin ligase c-Cbl, thereby inhibiting EGFR turnover in a CD109-dependent manner. The CD109-SMURF2-EGFR axis is shown to promote stemness, invasion, and proliferation in SCC cells induced by EGF. In summary, this research identifies CD109 as a regulatory switch that redirects EGFR from c-Cbl-mediated degradation to SMURF2-dependent stabilization, perpetuating oncogenic signaling. This previously unidentified regulatory pathway highlights the CD109-SMURF2 axis as a potential vulnerability for targeted intervention in EGFR-driven SCCs.",
  "summary": "Squamous cell carcinoma (SCC) remains difficult to treat, particularly in recurrent or metastatic disease. Although EGFR signaling is a well-established driver of SCC pathogenesis, mechanisms regulating its activity remain incompletely understood. CD109, a GPI-anchored glycoprotein frequently overexpressed in SCC, has been implicated in EGFR signaling, but its mechanisms remain poorly defined.…",
  "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."
}