Emerin Deregulation Links Nuclear Shape Instability to Metastatic Potential
Abstract
Abnormalities in nuclear shape are a well-known feature of cancer, but their contribution to malignant progression remains poorly understood. Here, we show that depletion of the cytoskeletal regulator, Diaphanous-related formin 3 (DIAPH3), or the nuclear membrane–associated proteins, lamin A/C, in prostate and breast cancer cells, induces nuclear shape instability, with a corresponding gain in malignant properties, including secretion of extracellular vesicles that contain genomic material. This transformation is characterized by a reduction and/or mislocalization of the inner nuclear membrane protein, emerin. Consistent with this, depletion of emerin evokes nuclear shape instability and promotes metastasis. By visualizing emerin localization, evidence for nuclear shape instability was observed in cultured tumor cells, in experimental models of prostate cancer, in human prostate cancer tissues, and in circulating tumor cells from patients with metastatic disease. Quantitation of emerin mislocalization discriminated cancer from benign tissue and correlated with disease progression in a prostate cancer cohort. Taken together, these results identify emerin as a mediator of nuclear shape stability in cancer and show that destabilization of emerin can promote metastasis.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 01, 2018
- Source ID
- 10.1158/0008-5472.can-18-0608
Entities
People
- Adel Eskaros
- Amy Rowat
- Andries Zijlstra
- Beatrice S Knudsen
- Chia-yi Chu
- Dolores Di Vizio
- Edwin M Posadas
- Hisashi Tanaka
- Hsian-Rong Tseng
- Jie-fu Chen
- Kenneth Steadman
- Leland W.k. Chung
- Mariana Reis Sobreiro
- Mariana Reis-sobreiro
- Mirja Rotinen
- Navjot Kaur Gill
- Samantha Morley
- Sungyong You
- Tatiana Novitskaya
- Wei Yang
Organizations
- Cedars-Sinai Medical Center
- National Institutes of Health
- National Science Foundation
- United States Department of Defense
- University of California
- University of California, Los Angeles
- Urology Care Foundation
- Vanderbilt University
- Veterans of Foreign Wars