TRF2 interaction with nuclear envelope is required for cell polarization and metastasis in triple negative breast cancer
The Telomere Repeat-Binding factor 2 (TRF2) contributes to cancer progression by both telomere-dependent and independent mechanisms, including immune escape and angiogenesis. Here, we found that TRF2, through its Basic domain, directly interacts with Emerin forming a complex, including Lamin A/C, Lamin B1, SUN1, and SUN2. Importantly, TRF2 association with the inner nuclear membrane is functional to the proper establishment of cell polarity, finally promoting productive 1D and 3D migration in triple negative breast cancer cells (TNBC). In line with this, a spontaneous model of TNBC metastasis, combined with intravital imaging, allowed us to demonstrate that TRF2 promotes cell migration at the primary tumor site and is required for the early steps of the metastatic cascade. In human breast cancers, aberrantly elevated TRF2 expression positively correlates with cancer progression, metastasis, and poor prognosis, identifying TRF2 as a potential target for novel therapeutic strategies against TNBC.
Authors
- Simonetta Buglioni (ORCID: https://orcid.org/0000-0002-5066-1523)
- Paola Ostano (ORCID: https://orcid.org/0000-0002-4000-2954)
- Manuela Porru (ORCID: https://orcid.org/0000-0002-6614-9110)
- Serena Di Vito (ORCID: https://orcid.org/0000-0001-8569-4918)
- Annamaria Biroccio (ORCID: https://orcid.org/0000-0003-3198-3532)
- Jeroen Lohuis
- Stefano Marchesi (ORCID: https://orcid.org/0000-0003-3973-133X)
- Qingsen Li (ORCID: https://orcid.org/0000-0002-7487-3133)
- Carlo Leonetti (ORCID: https://orcid.org/0000-0002-3526-7827)
- Giorgio Scita (ORCID: https://orcid.org/0000-0001-7984-1889)
- Jacco van Rheenen (ORCID: https://orcid.org/0000-0001-8175-1647)
- Roberto Dinami (ORCID: https://orcid.org/0000-0002-3585-3439)
- Andrea Sacconi (ORCID: https://orcid.org/0000-0002-8276-0438)
- Angela Rizzo (ORCID: https://orcid.org/0000-0001-5421-3085)
- Antonella Stoppacciaro (ORCID: https://orcid.org/0000-0002-8506-3363)
- Sara Iachettini (ORCID: https://orcid.org/0000-0002-9442-0326)
- Anna Di Benedetto (ORCID: https://orcid.org/0000-0002-9853-8671)
- Pasquale Zizza (ORCID: https://orcid.org/0000-0001-7281-6090)
- Erica Salvati (ORCID: https://orcid.org/0000-0002-3373-7442)
- Eleonora Petti (ORCID: https://orcid.org/0000-0001-8189-1906)
- Paolo Maiuri (ORCID: https://orcid.org/0000-0001-5079-445X)
- Carmen Maresca (ORCID: https://orcid.org/0000-0002-0778-8190)
- Flora Ascione
- Carmen D’Angelo
Institutions
- Università degli Studi della Tuscia (IT)
- University of Milan (IT)
- The Netherlands Cancer Institute (NL)
- Institute of Molecular Biology and Pathology (IT)
- Oncode Institute (NL)
- IFOM (IT)
- Fondazione Edo ed Elvo Tempia (IT)
- National Cancer Institute (MY)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- National Research Council (IT)
- European Institute of Oncology (IT)
- University of Naples Federico II (IT)
- Sapienza University of Rome (IT)
Publication Details
- Journal
- Cell Death and Disease
- Published
- 2025-03-30
- DOI
- https://doi.org/10.1038/s41419-025-07415-4
- Citations
- 1
- Primary Topic
- Nuclear Structure and Function
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Ministero della Salute
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Associazione Italiana per la Ricerca sul Cancro