Induction of autophagy during extracellular matrix detachment promotes cell survival. Export

@article{citeulike:4065929, abstract = {Autophagy has been proposed to promote cell death during lumen formation in three-dimensional mammary epithelial acini because numerous autophagic vacuoles are observed in the dying central cells during morphogenesis. Because these central cells die due to extracellular matrix (ECM) deprivation (anoikis), we have directly interrogated how matrix detachment regulates autophagy. Detachment induces autophagy in both nontumorigenic epithelial lines and in primary epithelial cells. RNA interference-mediated depletion of autophagy regulators (ATGs) inhibits detachment-induced autophagy, enhances apoptosis, and reduces clonogenic recovery after anoikis. Remarkably, matrix-detached cells still exhibit autophagy when apoptosis is blocked by Bcl-2 overexpression, and ATG depletion reduces the clonogenic survival of Bcl-2-expressing cells after detachment. Finally, stable reduction of ATG5 or ATG7 in MCF-10A acini enhances luminal apoptosis during morphogenesis and fails to elicit long-term luminal filling, even when combined with apoptotic inhibition mediated by Bcl-2 overexpression. Thus, autophagy promotes epithelial cell survival during anoikis, including detached cells harboring antiapoptotic lesions.}, author = {Fung, C. and Lock, R. and Gao, S. and Salas, E. and Debnath, J.}, citeulike-article-id = {4065929}, citeulike-linkout-0 = {http://dx.doi.org/10.1091/mbc.E07-10-1092}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18094039}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18094039}, doi = {10.1091/mbc.E07-10-1092}, issn = {1939-4586}, journal = {Molecular biology of the cell}, keywords = {autophagy, detachment, survival}, month = {March}, number = {3}, pages = {797--806}, posted-at = {2009-02-17 21:19:29}, priority = {2}, title = {Induction of autophagy during extracellular matrix detachment promotes cell survival.}, url = {http://dx.doi.org/10.1091/mbc.E07-10-1092}, volume = {19}, year = {2008} }

TY - JOUR ID - citeulike:4065929 L3 - citeulike-article-id:4065929 N2 - Autophagy has been proposed to promote cell death during lumen formation in three-dimensional mammary epithelial acini because numerous autophagic vacuoles are observed in the dying central cells during morphogenesis. Because these central cells die due to extracellular matrix (ECM) deprivation (anoikis), we have directly interrogated how matrix detachment regulates autophagy. Detachment induces autophagy in both nontumorigenic epithelial lines and in primary epithelial cells. RNA interference-mediated depletion of autophagy regulators (ATGs) inhibits detachment-induced autophagy, enhances apoptosis, and reduces clonogenic recovery after anoikis. Remarkably, matrix-detached cells still exhibit autophagy when apoptosis is blocked by Bcl-2 overexpression, and ATG depletion reduces the clonogenic survival of Bcl-2-expressing cells after detachment. Finally, stable reduction of ATG5 or ATG7 in MCF-10A acini enhances luminal apoptosis during morphogenesis and fails to elicit long-term luminal filling, even when combined with apoptotic inhibition mediated by Bcl-2 overexpression. Thus, autophagy promotes epithelial cell survival during anoikis, including detached cells harboring antiapoptotic lesions. IS - 3 JF - Molecular biology of the cell SN - 1939-4586 EP - 806 TI - Induction of autophagy during extracellular matrix detachment promotes cell survival. VL - 19 SP - 797 KW - autophagy KW - detachment KW - survival AU - Fung, C AU - Lock, R AU - Gao, S AU - Salas, E AU - Debnath, J PY - 2008/03// UR - http://dx.doi.org/10.1091/mbc.E07-10-1092 ER -