TY - JOUR
T1 - Cisplatin resistance can be curtailed by blunting Bnip3-mediated mitochondrial autophagy
AU - Vianello, Caterina
AU - Cocetta, Veronica
AU - Catanzaro, Daniela
AU - Dorn, Gerald W.
AU - De Milito, Angelo
AU - Rizzolio, Flavio
AU - Canzonieri, Vincenzo
AU - Cecchin, Erika
AU - Roncato, Rossana
AU - Toffoli, Giuseppe
AU - Quagliariello, Vincenzo
AU - Di Mauro, Annabella
AU - Losito, Simona
AU - Maurea, Nicola
AU - Cono, Scaffa
AU - Sales, Gabriele
AU - Scorrano, Luca
AU - Giacomello, Marta
AU - Montopoli, Monica
N1 - Funding Information:
We thank Drs. F. Caicci and F. Boldrin (Imaging Facility, Department of Biology, University of Padua) for EM sample preparation, and S. Schiavon (Imaging Facility, Department of Biology, University of Padua) for High Content Imaging at the HiTS@Unipd facility. PRID 2018, codice MONT_SID18_01 to M. M.; CARIPARO Starting Grant 2016 AIFbiol, STARS@Unipd Consolidator grant FIRMESs, MIUR PRIN 2017FS5SHL ?RADIUS? to M.G; NIH grant, R35 HL135736, to G.W.D.2nd.
Funding Information:
We thank Drs. F. Caicci and F. Boldrin (Imaging Facility, Department of Biology, University of Padua) for EM sample preparation, and S. Schiavon (Imaging Facility, Department of Biology, University of Padua) for High Content Imaging at the HiTS@Unipd facility. PRID 2018, codice MONT_SID18_01 to M. M.; CARIPARO Starting Grant 2016 AIFbiol, STARS@Unipd Consolidator grant FIRMESs, MIUR PRIN 2017FS5SHL “RADIUS” to M.G; NIH grant, R35 HL135736, to G.W.D.2nd.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/4
Y1 - 2022/4
N2 - Cisplatin (CDDP) is commonly used to treat a multitude of tumors including sarcomas, ovarian and cervical cancers. Despite recent investigations allowed to improve chemotherapy effectiveness, the molecular mechanisms underlying the development of CDDP resistance remain a major goal in cancer research. Here, we show that mitochondrial morphology and autophagy are altered in different CDDP resistant cancer cell lines. In CDDP resistant osteosarcoma and ovarian carcinoma, mitochondria are fragmented and closely juxtaposed to the endoplasmic reticulum; rates of mitophagy are also increased. Specifically, levels of the mitophagy receptor BNIP3 are higher both in resistant cells and in ovarian cancer patient samples resistant to platinum-based treatments. Genetic BNIP3 silencing or pharmacological inhibition of autophagosome formation re-sensitizes these cells to CDDP. Our study identifies inhibition of BNIP3-driven mitophagy as a potential therapeutic strategy to counteract CDDP resistance in ovarian carcinoma and osteosarcoma.
AB - Cisplatin (CDDP) is commonly used to treat a multitude of tumors including sarcomas, ovarian and cervical cancers. Despite recent investigations allowed to improve chemotherapy effectiveness, the molecular mechanisms underlying the development of CDDP resistance remain a major goal in cancer research. Here, we show that mitochondrial morphology and autophagy are altered in different CDDP resistant cancer cell lines. In CDDP resistant osteosarcoma and ovarian carcinoma, mitochondria are fragmented and closely juxtaposed to the endoplasmic reticulum; rates of mitophagy are also increased. Specifically, levels of the mitophagy receptor BNIP3 are higher both in resistant cells and in ovarian cancer patient samples resistant to platinum-based treatments. Genetic BNIP3 silencing or pharmacological inhibition of autophagosome formation re-sensitizes these cells to CDDP. Our study identifies inhibition of BNIP3-driven mitophagy as a potential therapeutic strategy to counteract CDDP resistance in ovarian carcinoma and osteosarcoma.
UR - http://www.scopus.com/inward/record.url?scp=85128801515&partnerID=8YFLogxK
U2 - 10.1038/s41419-022-04741-9
DO - 10.1038/s41419-022-04741-9
M3 - Article
C2 - 35459212
AN - SCOPUS:85128801515
SN - 2041-4889
VL - 13
JO - Cell Death and Disease
JF - Cell Death and Disease
IS - 4
M1 - 398
ER -