The Tetraspanin Tspan8 Associates with Endothelin Converting Enzyme ECE1 and Regulates Its Activity
Tspan8 is a member of the tetraspanins family of cell surface molecules. The ability of tetraspanins to organize membrane microdomains with other membrane molecules and interfere with their function suggests that they could act as surface integrators of external or internal signals. Among the first...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-09-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/15/19/4751 |
| _version_ | 1797576140523569152 |
|---|---|
| author | Yingying Zhu Julien Saint-Pol Viet Nguyen Eric Rubinstein Claude Boucheix Céline Greco |
| author_facet | Yingying Zhu Julien Saint-Pol Viet Nguyen Eric Rubinstein Claude Boucheix Céline Greco |
| author_sort | Yingying Zhu |
| collection | DOAJ |
| description | Tspan8 is a member of the tetraspanins family of cell surface molecules. The ability of tetraspanins to organize membrane microdomains with other membrane molecules and interfere with their function suggests that they could act as surface integrators of external or internal signals. Among the first identified tetraspanins, Tspan8 promotes tumor progression and metastasis, presumably by stimulating angiogenesis and cell motility. In patients, its expression on digestive tract tumors seems to be associated with a bad prognosis. We showed previously that Tspan8 associates with E-cadherin and EGFR and modulates their effects on cell motility. Using Mass spectrometry and western blot, we found a new partner, the endothelin converting enzyme ECE1, and showed that Tspan8 amplifies its activity of conversion of the endothelin-1 precursor bigET1 to endothelin. This was observed by transduction of the colon carcinoma cell line Isreco1, which does not express Tspan8, and on ileum tissue fragments of tspan8ko mice versus wild type mice. Given these results, Tspan8 appears to be a modulator of the endothelin axis, which could possibly be targeted in case of over-activity of endothelins in biological processes of tissues expressing Tspan8. |
| first_indexed | 2024-03-10T21:47:59Z |
| format | Article |
| id | doaj.art-ca7d5325fd184368aca2e7b56265476d |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T21:47:59Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-ca7d5325fd184368aca2e7b56265476d2023-11-19T14:10:02ZengMDPI AGCancers2072-66942023-09-011519475110.3390/cancers15194751The Tetraspanin Tspan8 Associates with Endothelin Converting Enzyme ECE1 and Regulates Its ActivityYingying Zhu0Julien Saint-Pol1Viet Nguyen2Eric Rubinstein3Claude Boucheix4Céline Greco5UMR-S 1004, SFR André Lwoff, Inserm, 94800 Villejuif, FranceUMR-S 1004, SFR André Lwoff, Inserm, 94800 Villejuif, FranceUniversité Paris Saclay, 91190 Gif-sur-Yvette, FranceUMR-S 1004, SFR André Lwoff, Inserm, 94800 Villejuif, FranceUniversité Paris Saclay, 91190 Gif-sur-Yvette, FranceDepartment of Pain and Palliative Care, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris (APHP), 75610 Paris, FranceTspan8 is a member of the tetraspanins family of cell surface molecules. The ability of tetraspanins to organize membrane microdomains with other membrane molecules and interfere with their function suggests that they could act as surface integrators of external or internal signals. Among the first identified tetraspanins, Tspan8 promotes tumor progression and metastasis, presumably by stimulating angiogenesis and cell motility. In patients, its expression on digestive tract tumors seems to be associated with a bad prognosis. We showed previously that Tspan8 associates with E-cadherin and EGFR and modulates their effects on cell motility. Using Mass spectrometry and western blot, we found a new partner, the endothelin converting enzyme ECE1, and showed that Tspan8 amplifies its activity of conversion of the endothelin-1 precursor bigET1 to endothelin. This was observed by transduction of the colon carcinoma cell line Isreco1, which does not express Tspan8, and on ileum tissue fragments of tspan8ko mice versus wild type mice. Given these results, Tspan8 appears to be a modulator of the endothelin axis, which could possibly be targeted in case of over-activity of endothelins in biological processes of tissues expressing Tspan8.https://www.mdpi.com/2072-6694/15/19/4751Tspan8endothelinECE1colorectal carcinoma |
| spellingShingle | Yingying Zhu Julien Saint-Pol Viet Nguyen Eric Rubinstein Claude Boucheix Céline Greco The Tetraspanin Tspan8 Associates with Endothelin Converting Enzyme ECE1 and Regulates Its Activity Cancers Tspan8 endothelin ECE1 colorectal carcinoma |
| title | The Tetraspanin Tspan8 Associates with Endothelin Converting Enzyme ECE1 and Regulates Its Activity |
| title_full | The Tetraspanin Tspan8 Associates with Endothelin Converting Enzyme ECE1 and Regulates Its Activity |
| title_fullStr | The Tetraspanin Tspan8 Associates with Endothelin Converting Enzyme ECE1 and Regulates Its Activity |
| title_full_unstemmed | The Tetraspanin Tspan8 Associates with Endothelin Converting Enzyme ECE1 and Regulates Its Activity |
| title_short | The Tetraspanin Tspan8 Associates with Endothelin Converting Enzyme ECE1 and Regulates Its Activity |
| title_sort | tetraspanin tspan8 associates with endothelin converting enzyme ece1 and regulates its activity |
| topic | Tspan8 endothelin ECE1 colorectal carcinoma |
| url | https://www.mdpi.com/2072-6694/15/19/4751 |
| work_keys_str_mv | AT yingyingzhu thetetraspanintspan8associateswithendothelinconvertingenzymeece1andregulatesitsactivity AT juliensaintpol thetetraspanintspan8associateswithendothelinconvertingenzymeece1andregulatesitsactivity AT vietnguyen thetetraspanintspan8associateswithendothelinconvertingenzymeece1andregulatesitsactivity AT ericrubinstein thetetraspanintspan8associateswithendothelinconvertingenzymeece1andregulatesitsactivity AT claudeboucheix thetetraspanintspan8associateswithendothelinconvertingenzymeece1andregulatesitsactivity AT celinegreco thetetraspanintspan8associateswithendothelinconvertingenzymeece1andregulatesitsactivity AT yingyingzhu tetraspanintspan8associateswithendothelinconvertingenzymeece1andregulatesitsactivity AT juliensaintpol tetraspanintspan8associateswithendothelinconvertingenzymeece1andregulatesitsactivity AT vietnguyen tetraspanintspan8associateswithendothelinconvertingenzymeece1andregulatesitsactivity AT ericrubinstein tetraspanintspan8associateswithendothelinconvertingenzymeece1andregulatesitsactivity AT claudeboucheix tetraspanintspan8associateswithendothelinconvertingenzymeece1andregulatesitsactivity AT celinegreco tetraspanintspan8associateswithendothelinconvertingenzymeece1andregulatesitsactivity |