Cancer-specific PERK signaling drives invasion and metastasis through CREB3L1
PERK signaling is required for cancer invasion and there is interest in targeting this pathway for therapy. Unfortunately, chemical inhibitors of PERK's kinase activity cause on-target side effects that have precluded their further development. One strategy for resolving this difficulty would b...
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Nature Publishing Group
2018
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| Online Access: | http://hdl.handle.net/1721.1/114663 https://orcid.org/0000-0003-1533-6730 https://orcid.org/0000-0002-2988-0537 https://orcid.org/0000-0002-4866-1145 https://orcid.org/0000-0002-9703-1780 |
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| author | Feng, Yu-Xiong Reinhardt, Ferenc Jin, Dexter X. Sokol, Ethan Samuel Miller, Daniel Handel Gupta, Piyush |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Feng, Yu-Xiong Reinhardt, Ferenc Jin, Dexter X. Sokol, Ethan Samuel Miller, Daniel Handel Gupta, Piyush |
| author_sort | Feng, Yu-Xiong |
| collection | MIT |
| description | PERK signaling is required for cancer invasion and there is interest in targeting this pathway for therapy. Unfortunately, chemical inhibitors of PERK's kinase activity cause on-target side effects that have precluded their further development. One strategy for resolving this difficulty would be to target downstream components of the pathway that specifically mediate PERK's pro-invasive and metastatic functions. Here we identify the transcription factor CREB3L1 as an essential mediator of PERK's pro-metastatic functions in breast cancer. CREB3L1 acts downstream of PERK, specifically in the mesenchymal subtype of triple-negative tumors, and its inhibition by genetic or pharmacological methods suppresses cancer cell invasion and metastasis. In patients with this tumor subtype, CREB3L1 expression is predictive of distant metastasis. These findings establish CREB3L1 as a key downstream mediator of PERK-driven metastasis and a druggable target for breast cancer therapy. |
| first_indexed | 2024-09-23T08:12:13Z |
| format | Article |
| id | mit-1721.1/114663 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T08:12:13Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1146632022-09-30T08:18:31Z Cancer-specific PERK signaling drives invasion and metastasis through CREB3L1 Feng, Yu-Xiong Reinhardt, Ferenc Jin, Dexter X. Sokol, Ethan Samuel Miller, Daniel Handel Gupta, Piyush Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Jin, Dexter X. Sokol, Ethan Samuel Miller, Daniel Handel Gupta, Piyush PERK signaling is required for cancer invasion and there is interest in targeting this pathway for therapy. Unfortunately, chemical inhibitors of PERK's kinase activity cause on-target side effects that have precluded their further development. One strategy for resolving this difficulty would be to target downstream components of the pathway that specifically mediate PERK's pro-invasive and metastatic functions. Here we identify the transcription factor CREB3L1 as an essential mediator of PERK's pro-metastatic functions in breast cancer. CREB3L1 acts downstream of PERK, specifically in the mesenchymal subtype of triple-negative tumors, and its inhibition by genetic or pharmacological methods suppresses cancer cell invasion and metastasis. In patients with this tumor subtype, CREB3L1 expression is predictive of distant metastasis. These findings establish CREB3L1 as a key downstream mediator of PERK-driven metastasis and a druggable target for breast cancer therapy. National Science Foundation (U.S.) (Grant 1122374) 2018-04-12T14:33:14Z 2018-04-12T14:33:14Z 2017-10 2016-12 2018-04-09T21:59:42Z Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/114663 Feng, Yu-Xiong et al. “Cancer-Specific PERK Signaling Drives Invasion and Metastasis through CREB3L1.” Nature Communications 8, 1 (October 2017): 1079 © 2017 The Authors https://orcid.org/0000-0003-1533-6730 https://orcid.org/0000-0002-2988-0537 https://orcid.org/0000-0002-4866-1145 https://orcid.org/0000-0002-9703-1780 http://dx.doi.org/10.1038/S41467-017-01052-Y Nature Communications Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature |
| spellingShingle | Feng, Yu-Xiong Reinhardt, Ferenc Jin, Dexter X. Sokol, Ethan Samuel Miller, Daniel Handel Gupta, Piyush Cancer-specific PERK signaling drives invasion and metastasis through CREB3L1 |
| title | Cancer-specific PERK signaling drives invasion and metastasis through CREB3L1 |
| title_full | Cancer-specific PERK signaling drives invasion and metastasis through CREB3L1 |
| title_fullStr | Cancer-specific PERK signaling drives invasion and metastasis through CREB3L1 |
| title_full_unstemmed | Cancer-specific PERK signaling drives invasion and metastasis through CREB3L1 |
| title_short | Cancer-specific PERK signaling drives invasion and metastasis through CREB3L1 |
| title_sort | cancer specific perk signaling drives invasion and metastasis through creb3l1 |
| url | http://hdl.handle.net/1721.1/114663 https://orcid.org/0000-0003-1533-6730 https://orcid.org/0000-0002-2988-0537 https://orcid.org/0000-0002-4866-1145 https://orcid.org/0000-0002-9703-1780 |
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