Journal article
WFDC3 inhibits tumor metastasis by promoting the ERβ-mediated transcriptional repression of TGFBR1 in colorectal cancer
Cell Death & Disease, Vol.14(7), pp.1-14
2023
PMCID: PMC10345115
PMID: 37443102
Appears in Cancer Research Cluster Research Collection
Abstract
Estrogen plays a protective role in colorectal cancer (CRC) and primarily functions through estrogen receptor β (ERβ). However, clinical strategies for CRC therapy associated with ERβ are still under investigation. Our discoveries identified WFDC3 as a tumor suppressor that facilitates estrogen-induced inhibition of metastasis through the ERβ/TGFBR1 signaling axis. WFDC3 interacts with ERβ and increases its protein stability by inhibiting its proteasome-dependent degradation. WFDC3 represses TGFBR1 expression through ERβ-mediated transcription. Blocking TGFβ signaling with galunisertib, a drug used in clinical trials that targets TGFBR1, impaired the migration of CRC cells induced by WFDC3 depletion. Moreover, there was clinical significance to WFDC3 in CRC, as CRC patients with high WFDC3 expression in tumor cells had favorable prognoses. Therefore, this work suggests that WFDC3 could be an indicator for therapies targeting the estrogen/ERβ pathway in CRC patients.
Details
- Title
- WFDC3 inhibits tumor metastasis by promoting the ERβ-mediated transcriptional repression of TGFBR1 in colorectal cancer
- Authors
- Tianqi Liu (Author) - Peking University Cancer HospitalMin Zhao (Author) - University of the Sunshine Coast, Queensland, School of Science, Technology and EngineeringLin Peng (Author) - Peking University Cancer HospitalJiangbo Chen (Author) - Peking University Cancer HospitalPu Xing (Author) - Peking University Cancer HospitalPin Gao (Author) - Peking University Cancer HospitalLei Chen (Author) - Peking University Cancer HospitalXiaowen Qiao (Author) - Peking University Cancer HospitalZaozao Wang (Author) - Peking University Cancer HospitalJiabo Di (Author) - Peking University Cancer HospitalHong Qu (Corresponding Author) - Peking UniversityBeihai Jiang (Corresponding Author) - Peking University Cancer HospitalXiangqian Su (Corresponding Author) - Peking University Cancer Hospital
- Publication details
- Cell Death & Disease, Vol.14(7), pp.1-14
- Publisher
- Nature Publishing Group
- Date published
- 2023
- DOI
- 10.1038/s41419-023-05956-0
- ISSN
- 2041-4889
- PMID
- 37443102; PMC10345115
- Copyright note
- This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Grant note
- 82173218, 82171720, 81872022, 31671375, and 31871339 / National Natural Science Foundation of China 5202008 / Beijing Natural Science Foundation 2017YFC1201200 / Research and Development Program of China ZYLX202116 / Beijing Hospitals Authority Clinical Medicine Development
- Organisation Unit
- University of the Sunshine Coast, Queensland; Cancer Research Cluster; School of Science, Technology and Engineering; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 99741796602621
- Output Type
- Journal article
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