Oncogenic DMTF1β promotes cancer cell motility by regulating autophagy through ULK1 stabilization
9 affiliations
- 1Institute of Tissue Medicine and Pathology, Division of Experimental Pathology University of Bern Switzerland
- 2Graduate School for Cellular and Biomedical Sciences University of Bern Switzerland
- 3Department of Biomedical Research, Division of Urology University of Bern Switzerland
- 4Department of Biology University of Fribourg Switzerland
- 5Department of Biomedical Research, Division of Tumor immunology University of Bern Switzerland
- 6Department of Medical Oncology, Inselspital, Bern University Hospital University of Bern Switzerland
- 7Department of Immunology and Microbiology The Scripps Research Institute La Jolla CA USA
- 8Department of Pediatrics, School of Medicine University of Washington Seattle WA USA
- 9Center for Immunity and Immunotherapies Seattle Children's Research Institute Seattle WA USA
Abstract
The cyclin D binding Myb‐like Transcription Factor 1 (DMTF1) is a haploinsufficient tumor suppressor in various tumors. Alternative splicing generates a dominant negative, truncated version of full‐length DMTF1α, named DMTF1β. DMTF1β has so far been described as an oncogene in breast cancer development. However, a clear understanding of how DMTF1β contributes to carcinogenesis remains unknown. Analyzing DMTF1β protein expression in breast cancer cell lines, as well as a highly metastatic prostate cancer cell line, confirmed a positive correlation between DMTF1β expression and tumorigenic potential. Specifically, knocking down DMTF1β in aggressive MDA‐MB‐231 breast and PC3MPRO4 prostate cancer cells significantly reduced wound closure and tissue invasion. β‐specific interactome and RNA‐sequencing studies in DMTF1β overexpressing and knockdown cells, respectively, suggest that DMTF1β expression is associated with the autophagy recycling pathway. Depleting DMTF1β levels in cancer cells significantly decreased autophagic flux. Moreover, inhibiting autophagy led to decreased migration of DMTF1β expressing breast cancer cells. Mechanistically, DMTF1β protein interacts with and stabilizes the key autophagy protein ULK1. In conclusion, we identified a novel function for the alternatively spliced DMTF1 gene product in autophagy‐dependent cancer cell motility.
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BibTeX
@article{xu2026oncogenic,
title = {{Oncogenic DMTF1β promotes cancer cell motility by regulating autophagy through ULK1 stabilization}},
author = {Jun Xu and Nicolas J. Niklaus and Anna M. Schläfli and Igor Tokarchuk and Magali Humbert and Federico La Manna and Bich Vu and David Maul and Ramin Radpour and Marianna Kruithof‐de Julio and Inti Zlobec and Jörn Dengjel and Bruce E. Torbett and Mario P. Tschan},
journal = {Molecular Oncology},
year = {2026},
month = may,
doi = {10.1002/1878-0261.70275},
url = {https://doi.org/10.1002/1878-0261.70275},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Oncogenic DMTF1β promotes cancer cell motility by regulating autophagy through ULK1 stabilization
AU - Jun Xu
AU - Nicolas J. Niklaus
AU - Anna M. Schläfli
AU - Igor Tokarchuk
AU - Magali Humbert
AU - Federico La Manna
AU - Bich Vu
AU - David Maul
AU - Ramin Radpour
AU - Marianna Kruithof‐de Julio
AU - Inti Zlobec
AU - Jörn Dengjel
AU - Bruce E. Torbett
AU - Mario P. Tschan
PY - 2026
DA - 2026/05/26
JO - Molecular Oncology
DO - 10.1002/1878-0261.70275
UR - https://doi.org/10.1002/1878-0261.70275
AB - The cyclin D binding Myb‐like Transcription Factor 1 (DMTF1) is a haploinsufficient tumor suppressor in various tumors. Alternative splicing generates a dominant negative, truncated version of full‐length DMTF1α, named DMTF1β. DMTF1β has so far been described as an oncogene in breast cancer development. However, a clear understanding of how DMTF1β contributes to carcinogenesis remains unknown. Analyzing DMTF1β protein expression in breast cancer cell lines, as well as a highly metastatic prostate cancer cell line, confirmed a positive correlation between DMTF1β expression and tumorigenic potential. Specifically, knocking down DMTF1β in aggressive MDA‐MB‐231 breast and PC3MPRO4 prostate cancer cells significantly reduced wound closure and tissue invasion. β‐specific interactome and RNA‐sequencing studies in DMTF1β overexpressing and knockdown cells, respectively, suggest that DMTF1β expression is associated with the autophagy recycling pathway. Depleting DMTF1β levels in cancer cells significantly decreased autophagic flux. Moreover, inhibiting autophagy led to decreased migration of DMTF1β expressing breast cancer cells. Mechanistically, DMTF1β protein interacts with and stabilizes the key autophagy protein ULK1. In conclusion, we identified a novel function for the alternatively spliced DMTF1 gene product in autophagy‐dependent cancer cell motility.
SN - 1574-7891
SN - 1878-0261
ER -