SMARCE1 is required for the invasive progression of in situ cancers
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...
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| Format: | Article |
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National Academy of Sciences (U.S.)
2018
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| Online Access: | http://hdl.handle.net/1721.1/113223 https://orcid.org/0000-0002-2988-0537 https://orcid.org/0000-0003-1533-6730 https://orcid.org/0000-0002-4866-1145 https://orcid.org/0000-0002-9703-1780 |
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| author | 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. Jaenisch, Rudolf Gupta, Piyush |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology 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. Jaenisch, Rudolf Gupta, Piyush |
| author_sort | Feng, Yu-Xiong |
| collection | MIT |
| description | 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 |
| first_indexed | 2024-09-23T16:55:08Z |
| format | Article |
| id | mit-1721.1/113223 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T16:55:08Z |
| publishDate | 2018 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/1132232021-07-01T02:10:25Z SMARCE1 is required for the invasive progression of in situ cancers 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. Jaenisch, Rudolf Gupta, Piyush Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Sokol, Ethan Samuel Jin, Dexter X. Miller, Daniel Handel Superville, Daphne A. Jaenisch, Rudolf Gupta, Piyush 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 National Science Foundation (U.S.) (Grant 1122374) 2018-01-18T17:31:27Z 2018-01-18T17:31:27Z 2017-04 2016-11 2018-01-16T19:42:08Z Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/113223 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 https://orcid.org/0000-0002-2988-0537 https://orcid.org/0000-0003-1533-6730 https://orcid.org/0000-0002-4866-1145 https://orcid.org/0000-0002-9703-1780 http://dx.doi.org/10.1073/PNAS.1703931114 Proceedings of the National Academy of Sciences 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. application/octet-stream National Academy of Sciences (U.S.) PNAS |
| spellingShingle | 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. Jaenisch, Rudolf Gupta, Piyush SMARCE1 is required for the invasive progression of in situ cancers |
| title | SMARCE1 is required for the invasive progression of in situ cancers |
| title_full | SMARCE1 is required for the invasive progression of in situ cancers |
| title_fullStr | SMARCE1 is required for the invasive progression of in situ cancers |
| title_full_unstemmed | SMARCE1 is required for the invasive progression of in situ cancers |
| title_short | SMARCE1 is required for the invasive progression of in situ cancers |
| title_sort | smarce1 is required for the invasive progression of in situ cancers |
| url | http://hdl.handle.net/1721.1/113223 https://orcid.org/0000-0002-2988-0537 https://orcid.org/0000-0003-1533-6730 https://orcid.org/0000-0002-4866-1145 https://orcid.org/0000-0002-9703-1780 |
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