View : 584 Download: 241
Small molecule activator of Nm23/NDPK as an inhibitor of metastasis
- Title
- Small molecule activator of Nm23/NDPK as an inhibitor of metastasis
- Authors
- Lee, Jae-Jin; Kim, Hwang Suk; Lee, Ji-Sun; Park, Jimin; Shin, Sang Chul; Song, Soonwha; Lee, Eunsun; Choi, Jung-Eun; Suh, Ji-Wan; Lee, Hongsoo; Kim, Eunice EunKyeong; Seo, Eun Kyoung; Shin, Dong Hae; Lee, Ho-Young; Lee, Hee-Yoon; Lee, Kong-Joo
- Ewha Authors
- 이공주; 서은경; 신동해
- SCOPUS Author ID
- 이공주; 서은경; 신동해
- Issue Date
- 2018
- Journal Title
- SCIENTIFIC REPORTS
- ISSN
- 2045-2322
- Citation
- SCIENTIFIC REPORTS vol. 8
- Publisher
- NATURE PUBLISHING GROUP
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Nm23-H1/NDPK-A is a tumor metastasis suppressor having NDP kinase (NDPK) activity. Nm23-H1 is positively associated with prolonged disease-free survival and good prognosis of cancer patients. Approaches to increasing the cellular levels of Nm23-H1 therefore have significance in the therapy of metastatic cancers. We found a small molecule, (+/-)-trans-3-(3,4-dimethoxyphenyl)-4-[(E)-3,4-dimethoxystyryl] cyclohex-1-ene, that activates Nm23, hereafter called NMac1. NMac1 directly binds to Nm23-H1 and increases its NDPK activity. Employing various NMac1 derivatives and hydrogen/deuterium mass spectrometry (HDX-MS), we identified the pharmacophore and mode of action of NMac1. We found that NMac1 binds to the C-terminal of Nm23-H1 and induces the NDPK activation through its allosteric conformational changes. NMac1-treated MDA-MB-231 breast cancer cells showed dramatic changes in morphology and actin-cytoskeletal organization following inhibition of Rac1 activation. NMac1 also suppressed invasion and migration in vitro, and metastasis in vivo, in a breast cancer mouse model. NMac1 as an activator of NDPK has potential as an anti-metastatic agent.
- DOI
- 10.1038/s41598-018-29101-6
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
- Files in This Item:
-
Small molecule activator.pdf(4.39 MB)
Download
- Export
- RIS (EndNote)
- XLS (Excel)
- XML