Tools
Tools
Wong, Ping-Pui, Munoz-Felix, Jose M, Hijazi, Maruan, Kim, Hyojin, Robinson, Stephen 
ORCID: https://orcid.org/0000-0002-6606-7588, De Luxan-Delgado, Beatriz, Rodiguez-Hernandez, Irene, Maiques, Oscar, Meng, Ya-Ming, Meng, Qiong, Bodrug, Natalia, Dukinfield, Matthew Scott, Reynolds, Louise E, Elia, George, Clear, Andrew, Harwood, Catherine, Wang, Yu, Campbell, James J, Singh, Rajinder, Zhang, Penglie, Schall, Thomas J, Matchett, Kylie P, Henderson, Neil, Szlosarek, Peter W, Dreger, Sally, Smith, Sally, Jones, Louise, Gribben, John G, Cutillas, Pedro R, Meier, Pascal, Sanz-Moreno, Victoria and Hodivala-Dilke, Kairbaan
(2020)
Cancer burden is controlled by mural cell-β3-integrin regulated crosstalk with tumor cells.
Cell, 181 (6).
1346-1363.e21.
ISSN 0092-8674
Preview |
PDF (CELL-D-18-01297_R4 (2)22)
- Accepted Version
Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (16MB) | Preview |
Abstract
Enhanced blood vessel (BV) formation is thought to drive tumor growth through elevated nutrient delivery. However, this observation has overlooked potential roles for mural cells in directly affecting tumor growth independent of BV function. Here we provide clinical data correlating high percentages of mural-β3-integrin-negative tumor BVs with increased tumor sizes but no effect on BV numbers. Mural-β3-integrin loss also enhances tumor growth in implanted and autochthonous mouse tumor models with no detectable effects on BV numbers or function. At a molecular level, mural-cell β3-integrin loss enhances signaling via FAK-p-HGFR-p-Akt-p-p65, driving CXCL1, CCL2, and TIMP-1 production. In particular, mural-cell-derived CCL2 stimulates tumor cell MEK1-ERK1/2-ROCK2-dependent signaling and enhances tumor cell survival and tumor growth. Overall, our data indicate that mural cells can control tumor growth via paracrine signals regulated by β3-integrin, providing a previously unrecognized mechanism of cancer growth control.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | mural cell,paracrine,β3-integrin,biochemistry, genetics and molecular biology(all),sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1300 |
| Faculty \ School: | Faculty of Science > School of Biological Sciences |
| UEA Research Groups: | Faculty of Science > Research Groups > Cells and Tissues Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 02 Jun 2020 00:15 |
| Last Modified: | 23 Jan 2024 01:34 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/75425 |
| DOI: | 10.1016/j.cell.2020.02.003 |
Downloads
Downloads per month over past year
Actions (login required)
 |
View Item |