SMARCE1 is required for the invasive progression of in situ cancers
Name
SMARCE1 is required for the invasive progression of in situ cancers
Size
1.54 MB
Format
Unknown
Checksum (MD5)
93a289ba7b1fe5cf4bd6ba708007ef2e
Author(s)
Feng, Yu-Xiong
Tizabi, Minu D.
Cohen, Malkiel A.
Sanduja, Sandhya
Reinhardt, Ferenc
Pandey, Jai
Sokol, Ethan Samuel
Jin, Dexter X.
Miller, Daniel Handel
Superville, Daphne A.
Date Issued
April 2017
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Sokol, Ethan S. et al. “SMARCE1 Is Required for the Invasive Progression of in Situ Cancers.” Proceedings of the National Academy of Sciences 114, 16 (April 2017): 4153–4158 © 2017 National Academy of Sciences
Version
Final published version
Abstract
Advances in mammography have sparked an exponential increase in the detection of early-stage breast lesions, most commonly ductal carcinoma in situ (DCIS). More than 50% of DCIS lesions are benign and will remain indolent, never progressing to invasive cancers. However, the factors that promote DCIS invasion remain poorly understood. Here, we show that SMARCE1 is required for the invasive progression of DCIS and other early-stage tumors. We show that SMARCE1 drives invasion by regulating the expression of secreted proteases that degrade basement membrane, an ECM barrier surrounding all epithelial tissues. In functional studies, SMARCE1 promotes invasion of in situ cancers growing within primary human mammary tissues and is also required for metastasis in vivo. Mechanistically, SMARCE1 drives invasion by forming a SWI/SNF-independent complex with the transcription factor ILF3. In patients diagnosed with early-stage cancers, SMARCE1 expression is a strong predictor of eventual relapse and metastasis. Collectively, these findings establish SMARCE1 as a key driver of invasive progression in early-stage tumors. Keywords: DCIS; invasive progression; biomarker; SMARCE1
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/PNAS.1703931114
