MAGI1 inhibits the AMOTL2/p38 stress pathway and prevents luminal breast tumorigenesis
Abstract Alterations to cell polarization or to intercellular junctions are often associated with epithelial cancer progression, including breast cancers (BCa). We show here that the loss of the junctional scaffold protein MAGI1 is associated with bad prognosis in luminal BCa, and promotes tumorigen...
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Nature Portfolio
2021
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oai:doaj.org-article:360a50e2dc1748519708e862bd8280142021-12-02T13:19:29ZMAGI1 inhibits the AMOTL2/p38 stress pathway and prevents luminal breast tumorigenesis10.1038/s41598-021-85056-12045-2322https://doaj.org/article/360a50e2dc1748519708e862bd8280142021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85056-1https://doaj.org/toc/2045-2322Abstract Alterations to cell polarization or to intercellular junctions are often associated with epithelial cancer progression, including breast cancers (BCa). We show here that the loss of the junctional scaffold protein MAGI1 is associated with bad prognosis in luminal BCa, and promotes tumorigenesis. E-cadherin and the actin binding scaffold AMOTL2 accumulate in MAGI1 deficient cells which are subjected to increased stiffness. These alterations are associated with low YAP activity, the terminal Hippo-pathway effector, but with an elevated ROCK and p38 Stress Activated Protein Kinase activities. Blocking ROCK prevented p38 activation, suggesting that MAGI1 limits p38 activity in part through releasing actin strength. Importantly, the increased tumorigenicity of MAGI1 deficient cells is rescued in the absence of AMOTL2 or after inhibition of p38, demonstrating that MAGI1 acts as a tumor-suppressor in luminal BCa by inhibiting an AMOTL2/p38 stress pathway.Diala KantarEmilie Bousquet MurMaicol ManciniVera SlaninovaYezza Ben SalahLuca CostaElodie ForestPatrice LassusCharles GéminardFlorence Boissière-MichotBéatrice OrsettiCharles TheilletJacques ColingeChristine BenistantAntonio MaraverLisa Heron-MilhavetAlexandre DjianeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-20 (2021) |
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Medicine R Science Q Diala Kantar Emilie Bousquet Mur Maicol Mancini Vera Slaninova Yezza Ben Salah Luca Costa Elodie Forest Patrice Lassus Charles Géminard Florence Boissière-Michot Béatrice Orsetti Charles Theillet Jacques Colinge Christine Benistant Antonio Maraver Lisa Heron-Milhavet Alexandre Djiane MAGI1 inhibits the AMOTL2/p38 stress pathway and prevents luminal breast tumorigenesis |
| description |
Abstract Alterations to cell polarization or to intercellular junctions are often associated with epithelial cancer progression, including breast cancers (BCa). We show here that the loss of the junctional scaffold protein MAGI1 is associated with bad prognosis in luminal BCa, and promotes tumorigenesis. E-cadherin and the actin binding scaffold AMOTL2 accumulate in MAGI1 deficient cells which are subjected to increased stiffness. These alterations are associated with low YAP activity, the terminal Hippo-pathway effector, but with an elevated ROCK and p38 Stress Activated Protein Kinase activities. Blocking ROCK prevented p38 activation, suggesting that MAGI1 limits p38 activity in part through releasing actin strength. Importantly, the increased tumorigenicity of MAGI1 deficient cells is rescued in the absence of AMOTL2 or after inhibition of p38, demonstrating that MAGI1 acts as a tumor-suppressor in luminal BCa by inhibiting an AMOTL2/p38 stress pathway. |
| format |
article |
| author |
Diala Kantar Emilie Bousquet Mur Maicol Mancini Vera Slaninova Yezza Ben Salah Luca Costa Elodie Forest Patrice Lassus Charles Géminard Florence Boissière-Michot Béatrice Orsetti Charles Theillet Jacques Colinge Christine Benistant Antonio Maraver Lisa Heron-Milhavet Alexandre Djiane |
| author_facet |
Diala Kantar Emilie Bousquet Mur Maicol Mancini Vera Slaninova Yezza Ben Salah Luca Costa Elodie Forest Patrice Lassus Charles Géminard Florence Boissière-Michot Béatrice Orsetti Charles Theillet Jacques Colinge Christine Benistant Antonio Maraver Lisa Heron-Milhavet Alexandre Djiane |
| author_sort |
Diala Kantar |
| title |
MAGI1 inhibits the AMOTL2/p38 stress pathway and prevents luminal breast tumorigenesis |
| title_short |
MAGI1 inhibits the AMOTL2/p38 stress pathway and prevents luminal breast tumorigenesis |
| title_full |
MAGI1 inhibits the AMOTL2/p38 stress pathway and prevents luminal breast tumorigenesis |
| title_fullStr |
MAGI1 inhibits the AMOTL2/p38 stress pathway and prevents luminal breast tumorigenesis |
| title_full_unstemmed |
MAGI1 inhibits the AMOTL2/p38 stress pathway and prevents luminal breast tumorigenesis |
| title_sort |
magi1 inhibits the amotl2/p38 stress pathway and prevents luminal breast tumorigenesis |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/360a50e2dc1748519708e862bd828014 |
| work_keys_str_mv |
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