Nhibition of the Autophagic Flux by Salinomycin in Breast Cancer Stem-Like/Progenitor Cells Interferes with Their Maintenance
BAsic ReseARch PAPeR
BAsic ReseARch PAPeR
Autophagy 9:5, 1–16; May 2013; © 2013 Landes Bioscience
Inhibition of the autophagic flux by salinomycin in breast cancer stem-like/progenitor cells interferes with their maintenance
Wen Yue,1,2,† Ahmed hamaï,1,2,† Giovanni Tonelli,1,2 chantal Bauvy,1,2 Valérie Nicolas,2,3 hugo Tharinger,2,3 Patrice codogno1,2 and Maryam Mehrpour1,2,*
1
†
These authors contributed equally to this work.
Keywords: breast cancer stem-like/progenitor cell, salinomycin, autophagy, cell death, lysosome Abbreviations: ACTB, actin, beta; ATG12, autophagy-related 12; ATG5, autophagy-related 5; ATG16L1, autophagy-related ATG16L1; ALDH1, aldehyde dehydrogenase 1; Baf, bafilomycin A1; BECN1, Beclin 1, autophagy related; BCSCs, breast cancer stem-like /progenitor cells; CASP3, caspase 3; CASP8, caspase 8, apoptosis-related cysteine peptidase; CTNNB1, catenin (cadherin-associated protein), beta 1; CTS, cathepsin; EPCAM, epithelial cell adhesion molecule; LRP6, lipoprotein receptor related protein; LC3, microtubule-associated protein 1 light chain 3B; MTORC1, the mechanistic target of rapamycin complex 1; Nig, nigericin; PAS, phagophore assembly site; AO, acridine orange; RAB7A, member RAS oncogene family; ROS, reactive oxygen species; RPTOR, regulatory associated protein of MTOR, complex 1; Sal, salinomycin; TUBB, β-tubulin; WNT1, wingless-type MMTV integration site family
Breast cancer tissue contains a small population of cells that have the ability to self-renew; these cells are known as cancer stem-like cells (cscs). We have recently shown that autophagy is essential for the tumorigenicity of these cscs. salinomycin (sal), a K+/h+ ionophore, has recently been shown to be at least 100 times more effective than paclitaxel in reducing the proportion of breast cscs. however, its mechanisms of action are still unclear. We show here that sal blocked both autophagy flux and lysosomal proteolytic activity in both cscs and non-cscs
BAsic ReseARch PAPeR
Autophagy 9:5, 1–16; May 2013; © 2013 Landes Bioscience
Inhibition of the autophagic flux by salinomycin in breast cancer stem-like/progenitor cells interferes with their maintenance
Wen Yue,1,2,† Ahmed hamaï,1,2,† Giovanni Tonelli,1,2 chantal Bauvy,1,2 Valérie Nicolas,2,3 hugo Tharinger,2,3 Patrice codogno1,2 and Maryam Mehrpour1,2,*
1
†
These authors contributed equally to this work.
Keywords: breast cancer stem-like/progenitor cell, salinomycin, autophagy, cell death, lysosome Abbreviations: ACTB, actin, beta; ATG12, autophagy-related 12; ATG5, autophagy-related 5; ATG16L1, autophagy-related ATG16L1; ALDH1, aldehyde dehydrogenase 1; Baf, bafilomycin A1; BECN1, Beclin 1, autophagy related; BCSCs, breast cancer stem-like /progenitor cells; CASP3, caspase 3; CASP8, caspase 8, apoptosis-related cysteine peptidase; CTNNB1, catenin (cadherin-associated protein), beta 1; CTS, cathepsin; EPCAM, epithelial cell adhesion molecule; LRP6, lipoprotein receptor related protein; LC3, microtubule-associated protein 1 light chain 3B; MTORC1, the mechanistic target of rapamycin complex 1; Nig, nigericin; PAS, phagophore assembly site; AO, acridine orange; RAB7A, member RAS oncogene family; ROS, reactive oxygen species; RPTOR, regulatory associated protein of MTOR, complex 1; Sal, salinomycin; TUBB, β-tubulin; WNT1, wingless-type MMTV integration site family
Breast cancer tissue contains a small population of cells that have the ability to self-renew; these cells are known as cancer stem-like cells (cscs). We have recently shown that autophagy is essential for the tumorigenicity of these cscs. salinomycin (sal), a K+/h+ ionophore, has recently been shown to be at least 100 times more effective than paclitaxel in reducing the proportion of breast cscs. however, its mechanisms of action are still unclear. We show here that sal blocked both autophagy flux and lysosomal proteolytic activity in both cscs and non-cscs