mTOR Repression in Response to Amino Acid Starvation Promotes ECM Degradation Through MT1‐MMP Endocytosis Arrest
Abstract Under conditions of starvation, normal and tumor epithelial cells can rewire their metabolism toward the consumption of extracellular proteins, including extracellular matrix‐derived components as nutrient sources. The mechanism of pericellular matrix degradation by starved cells has been l...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-09-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202101614 |
| _version_ | 1818358476799213568 |
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| author | Cecilia Colombero David Remy Sandra Antoine‐Bally Anne‐Sophie Macé Pedro Monteiro Nadia ElKhatib Margot Fournier Ahmed Dahmani Elodie Montaudon Guillaume Montagnac Elisabetta Marangoni Philippe Chavrier |
| author_facet | Cecilia Colombero David Remy Sandra Antoine‐Bally Anne‐Sophie Macé Pedro Monteiro Nadia ElKhatib Margot Fournier Ahmed Dahmani Elodie Montaudon Guillaume Montagnac Elisabetta Marangoni Philippe Chavrier |
| author_sort | Cecilia Colombero |
| collection | DOAJ |
| description | Abstract Under conditions of starvation, normal and tumor epithelial cells can rewire their metabolism toward the consumption of extracellular proteins, including extracellular matrix‐derived components as nutrient sources. The mechanism of pericellular matrix degradation by starved cells has been largely overlooked. Here it is shown that matrix degradation by breast and pancreatic tumor cells and patient‐derived xenograft explants increases by one order of magnitude upon amino acid and growth factor deprivation. In addition, it is found that collagenolysis requires the invadopodia components, TKS5, and the transmembrane metalloproteinase, MT1‐MMP, which are key to the tumor invasion program. Increased collagenolysis is controlled by mTOR repression upon nutrient depletion or pharmacological inhibition by rapamycin. The results reveal that starvation hampers clathrin‐mediated endocytosis, resulting in MT1‐MMP accumulation in arrested clathrin‐coated pits. The study uncovers a new mechanism whereby mTOR repression in starved cells leads to the repurposing of abundant plasma membrane clathrin‐coated pits into robust ECM‐degradative assemblies. |
| first_indexed | 2024-12-13T20:29:37Z |
| format | Article |
| id | doaj.art-4854c4ce62ba4e178b9497279d33d1b4 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-13T20:29:37Z |
| publishDate | 2021-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-4854c4ce62ba4e178b9497279d33d1b42022-12-21T23:32:27ZengWileyAdvanced Science2198-38442021-09-01817n/an/a10.1002/advs.202101614mTOR Repression in Response to Amino Acid Starvation Promotes ECM Degradation Through MT1‐MMP Endocytosis ArrestCecilia Colombero0David Remy1Sandra Antoine‐Bally2Anne‐Sophie Macé3Pedro Monteiro4Nadia ElKhatib5Margot Fournier6Ahmed Dahmani7Elodie Montaudon8Guillaume Montagnac9Elisabetta Marangoni10Philippe Chavrier11Institut Curie PSL Research University CNRS UMR 144 Paris 75005 FranceInstitut Curie PSL Research University CNRS UMR 144 Paris 75005 FranceInstitut Curie PSL Research University CNRS UMR 144 Paris 75005 FranceInstitut Curie PSL Research University CNRS UMR 144 Paris 75005 FranceInstitut Curie PSL Research University CNRS UMR 144 Paris 75005 FranceGustave Roussy Institute Université Paris‐Saclay INSERM U1279 Villejuif 94805 FranceInstitut Curie PSL Research University CNRS UMR 144 Paris 75005 FranceTranslational Research Department Institut Curie PSL Research University Paris 75005 FranceTranslational Research Department Institut Curie PSL Research University Paris 75005 FranceGustave Roussy Institute Université Paris‐Saclay INSERM U1279 Villejuif 94805 FranceTranslational Research Department Institut Curie PSL Research University Paris 75005 FranceInstitut Curie PSL Research University CNRS UMR 144 Paris 75005 FranceAbstract Under conditions of starvation, normal and tumor epithelial cells can rewire their metabolism toward the consumption of extracellular proteins, including extracellular matrix‐derived components as nutrient sources. The mechanism of pericellular matrix degradation by starved cells has been largely overlooked. Here it is shown that matrix degradation by breast and pancreatic tumor cells and patient‐derived xenograft explants increases by one order of magnitude upon amino acid and growth factor deprivation. In addition, it is found that collagenolysis requires the invadopodia components, TKS5, and the transmembrane metalloproteinase, MT1‐MMP, which are key to the tumor invasion program. Increased collagenolysis is controlled by mTOR repression upon nutrient depletion or pharmacological inhibition by rapamycin. The results reveal that starvation hampers clathrin‐mediated endocytosis, resulting in MT1‐MMP accumulation in arrested clathrin‐coated pits. The study uncovers a new mechanism whereby mTOR repression in starved cells leads to the repurposing of abundant plasma membrane clathrin‐coated pits into robust ECM‐degradative assemblies.https://doi.org/10.1002/advs.202101614breast cancerclathrin‐mediated endocytosisextracellular matrixinvadopodiaMT1‐MMPmTOR |
| spellingShingle | Cecilia Colombero David Remy Sandra Antoine‐Bally Anne‐Sophie Macé Pedro Monteiro Nadia ElKhatib Margot Fournier Ahmed Dahmani Elodie Montaudon Guillaume Montagnac Elisabetta Marangoni Philippe Chavrier mTOR Repression in Response to Amino Acid Starvation Promotes ECM Degradation Through MT1‐MMP Endocytosis Arrest Advanced Science breast cancer clathrin‐mediated endocytosis extracellular matrix invadopodia MT1‐MMP mTOR |
| title | mTOR Repression in Response to Amino Acid Starvation Promotes ECM Degradation Through MT1‐MMP Endocytosis Arrest |
| title_full | mTOR Repression in Response to Amino Acid Starvation Promotes ECM Degradation Through MT1‐MMP Endocytosis Arrest |
| title_fullStr | mTOR Repression in Response to Amino Acid Starvation Promotes ECM Degradation Through MT1‐MMP Endocytosis Arrest |
| title_full_unstemmed | mTOR Repression in Response to Amino Acid Starvation Promotes ECM Degradation Through MT1‐MMP Endocytosis Arrest |
| title_short | mTOR Repression in Response to Amino Acid Starvation Promotes ECM Degradation Through MT1‐MMP Endocytosis Arrest |
| title_sort | mtor repression in response to amino acid starvation promotes ecm degradation through mt1 mmp endocytosis arrest |
| topic | breast cancer clathrin‐mediated endocytosis extracellular matrix invadopodia MT1‐MMP mTOR |
| url | https://doi.org/10.1002/advs.202101614 |
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