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TRF2 interaction with nuclear envelope is required for cell polarization and metastasis in triple negative breast cancer
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TRF2 interaction with nuclear envelope is required for cell polarization and metastasis in triple negative breast cancer
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Journal Article
TRF2 interaction with nuclear envelope is required for cell polarization and metastasis in triple negative breast cancer
2025
Overview
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.
Publisher
Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
Subject
/ 13/51
/ 13/89
/ 14
/ 14/19
/ 14/3
/ 38/32
/ 42/109
/ 59/5
/ 64/60
/ 96/2
/ Animals
/ Biomedical and Life Sciences
/ Cancer
/ Female
/ Humans
/ Intracellular Signaling Peptides and Proteins
/ Membrane Proteins - genetics
/ Membrane Proteins - metabolism
/ Mice
/ Microtubule-Associated Proteins
/ Mutation
/ Nuclear Envelope - metabolism
/ Nuclear Proteins - metabolism
/ Oncology
/ Proteins
/ Telomeric Repeat Binding Protein 2 - genetics
/ Telomeric Repeat Binding Protein 2 - metabolism
/ Triple Negative Breast Neoplasms - genetics
/ Triple Negative Breast Neoplasms - metabolism
/ Triple Negative Breast Neoplasms - pathology
/ Yeast
