Oncogenic DMTF1β promotes cancer cell motility by regulating autophagy through ULK1 stabilization

Jun Xu1,2, Nicolas J Niklaus1,2, Anna M Schläfli1

  • 1Institute of Tissue Medicine and Pathology, Division of Experimental Pathology, University of Bern, Switzerland.

Molecular Oncology
|May 26, 2026
PubMed

Insights

The truncated DMTF1β protein drives cancer cell movement by stabilizing ULK1, a key player in the autophagy pathway. This finding reveals a novel mechanism in cancer progression and motility.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • The cyclin D binding Myb-like Transcription Factor 1 (DMTF1) acts as a tumor suppressor.
  • Alternative splicing produces DMTF1β, a truncated, dominant-negative form implicated as an oncogene in breast cancer.
  • The precise role of DMTF1β in carcinogenesis is not fully understood.

Purpose of the Study:

  • To investigate the role of DMTF1β in cancer progression and identify its molecular mechanisms.
  • To explore the association between DMTF1β expression and cancer cell motility.
  • To elucidate the functional link between DMTF1β and the autophagy pathway.

Main Methods:

  • Analysis of DMTF1β protein expression in breast and prostate cancer cell lines.
  • Gene knockdown experiments to assess the impact of DMTF1β on cell migration and invasion.
  • Interactome and RNA-sequencing studies to identify DMTF1β-associated pathways.
  • Investigation of DMTF1β's interaction with autophagy-related proteins, specifically ULK1.

Main Results:

  • DMTF1β expression positively correlates with tumorigenic potential in cancer cell lines.
  • Knockdown of DMTF1β significantly reduced migration and invasion in aggressive breast and prostate cancer cells.
  • DMTF1β expression is linked to the autophagy pathway, and its depletion impairs autophagic flux.
  • DMTF1β interacts with and stabilizes the autophagy protein ULK1, promoting cancer cell motility.

Conclusions:

  • DMTF1β promotes cancer cell motility through a novel mechanism involving the autophagy pathway.
  • Stabilization of ULK1 by DMTF1β is a key step in enhancing autophagy-dependent cancer cell migration.
  • This study identifies an important role for alternatively spliced DMTF1 variants in cancer progression.

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