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1. Tissue fluidification promotes a cGAS–STING cytosolic DNA response in invasive breast cancer

Author

Frittoli, Emanuela, Palamidessi, Andrea, Iannelli, Fabio, Zanardi, Federica, Villa, Stefano, Barzaghi, Leonardo, Abdo, Hind, Cancila, Valeria, Beznoussenko, Galina V., Della Chiara, Giulia, Pagani, Massimiliano, Malinverno, Chiara, Bhattacharya, Dipanjan, Pisati, Federica, Yu, Weimiao, Galimberti, Viviana, Bonizzi, Giuseppina, Martini, Emanuele, Mironov, Alexander A., Gioia, Ubaldo, Ascione, Flora, Li, Qingsen, Havas, Kristina, Magni, Serena, Lavagnino, Zeno, Pennacchio, Fabrizio Andrea, Maiuri, Paolo, Caponi, Silvia, Mattarelli, Maurizio, Martino, Sabata, d’Adda di Fagagna, Fabrizio, Rossi, Chiara, Lucioni, Marco, Tancredi, Richard, Pedrazzoli, Paolo, Vecchione, Andrea, Petrini, Cristiano, Ferrari, Francesco, Lanzuolo, Chiara, Bertalot, Giovanni, Nader, Guilherme, Foiani, Marco, Piel, Matthieu, Cerbino, Roberto, Giavazzi, Fabio, Tripodo, Claudio, and Scita, Giorgio

Published
2023
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2. Trop-2, Na+/K+ ATPase, CD9, PKCα, cofilin assemble a membrane signaling super-complex that drives colorectal cancer growth and invasion

Author

Guerra, Emanuela, Relli, Valeria, Ceci, Martina, Tripaldi, Romina, Simeone, Pasquale, Aloisi, Anna Laura, Pantalone, Ludovica, La Sorda, Rossana, Lattanzio, Rossano, Sacchetti, Andrea, Havas, Kristina, Guarnieri, Simone, Vergara, Daniele, Fournier, Isabelle, Salzet, Michel, Tinari, Nicola, Piantelli, Mauro, Trerotola, Marco, and Alberti, Saverio

Published
2022
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3. Author Correction: Tissue fluidification promotes a cGAS–STING cytosolic DNA response in invasive breast cancer

Author

Frittoli, Emanuela, Palamidessi, Andrea, Iannelli, Fabio, Zanardi, Federica, Villa, Stefano, Barzaghi, Leonardo, Abdo, Hind, Cancila, Valeria, Beznoussenko, Galina V., Della Chiara, Giulia, Pagani, Massimiliano, Malinverno, Chiara, Bhattacharya, Dipanjan, Pisati, Federica, Yu, Weimiao, Galimberti, Viviana, Bonizzi, Giuseppina, Martini, Emanuele, Mironov, Alexander A., Gioia, Ubaldo, Ascione, Flora, Li, Qingsen, Havas, Kristina, Magni, Serena, Lavagnino, Zeno, Pennacchio, Fabrizio Andrea, Maiuri, Paolo, Caponi, Silvia, Mattarelli, Maurizio, Martino, Sabata, d’Adda di Fagagna, Fabrizio, Rossi, Chiara, Lucioni, Marco, Tancredi, Richard, Pedrazzoli, Paolo, Vecchione, Andrea, Petrini, Cristiano, Ferrari, Francesco, Lanzuolo, Chiara, Bertalot, Giovanni, Nader, Guilherme, Foiani, Marco, Piel, Matthieu, Cerbino, Roberto, Giavazzi, Fabio, Tripodo, Claudio, and Scita, Giorgio

Published
2023
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4. Acetyl-CoA carboxylase 1 controls a lipid droplet–peroxisome axis and is a vulnerability of endocrine-resistant ER + breast cancer

Author

Bacci, Marina, primary, Lorito, Nicla, additional, Smiriglia, Alfredo, additional, Subbiani, Angela, additional, Bonechi, Francesca, additional, Comito, Giuseppina, additional, Morriset, Ludivine, additional, El Botty, Rania, additional, Benelli, Matteo, additional, López-Velazco, Joanna I., additional, Caffarel, Maria M., additional, Urruticoechea, Ander, additional, Sflomos, George, additional, Malorni, Luca, additional, Corsini, Michela, additional, Ippolito, Luigi, additional, Giannoni, Elisa, additional, Meattini, Icro, additional, Matafora, Vittoria, additional, Havas, Kristina, additional, Bachi, Angela, additional, Chiarugi, Paola, additional, Marangoni, Elisabetta, additional, and Morandi, Andrea, additional

Published
2024
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5. Clonal cooperation through soluble metabolite exchange facilitates metastatic outgrowth by modulating Allee effect

Author

Hershey, Benjamin J., primary, Barozzi, Sara, additional, Orsenigo, Fabrizio, additional, Pompei, Simone, additional, Iannelli, Fabio, additional, Kamrad, Stephan, additional, Matafora, Vittoria, additional, Pisati, Federica, additional, Calabrese, Ludovico, additional, Fragale, Giuseppe, additional, Salvadori, Giulia, additional, Martini, Emanuele, additional, Totaro, Maria Grazia, additional, Magni, Serena, additional, Guan, Rui, additional, Parazzoli, Dario, additional, Maiuri, Paolo, additional, Bachi, Angela, additional, Patil, Kiran R., additional, Cosentino Lagomarsino, Marco, additional, and Havas, Kristina M., additional

Published
2023
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6. Data from 3D-Informed Targeting of the Trop-2 Signal-Activation Site Drives Selective Cancer Vulnerability

Author

Guerra, Emanuela, primary, Trerotola, Marco, primary, Relli, Valeria, primary, Lattanzio, Rossano, primary, Tripaldi, Romina, primary, Ceci, Martina, primary, Boujnah, Khouloud, primary, Pantalone, Ludovica, primary, Sacchetti, Andrea, primary, Havas, Kristina M., primary, Simeone, Pasquale, primary, Travali, Nicole, primary, Querzoli, Patrizia, primary, Pedriali, Massimo, primary, Roversi, Pietro, primary, Iezzi, Manuela, primary, Tinari, Nicola, primary, Antolini, Laura, primary, and Alberti, Saverio, primary

Published
2023
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7. Movie S1 from 3D-Informed Targeting of the Trop-2 Signal-Activation Site Drives Selective Cancer Vulnerability

Author

Guerra, Emanuela, primary, Trerotola, Marco, primary, Relli, Valeria, primary, Lattanzio, Rossano, primary, Tripaldi, Romina, primary, Ceci, Martina, primary, Boujnah, Khouloud, primary, Pantalone, Ludovica, primary, Sacchetti, Andrea, primary, Havas, Kristina M., primary, Simeone, Pasquale, primary, Travali, Nicole, primary, Querzoli, Patrizia, primary, Pedriali, Massimo, primary, Roversi, Pietro, primary, Iezzi, Manuela, primary, Tinari, Nicola, primary, Antolini, Laura, primary, and Alberti, Saverio, primary

Published
2023
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8. ATR is essential for preservation of cell mechanics and nuclear integrity during interstitial migration

Author

Kidiyoor, Gururaj Rao, Li, Qingsen, Bastianello, Giulia, Bruhn, Christopher, Giovannetti, Irene, Mohamood, Adhil, Beznoussenko, Galina V., Mironov, Alexandre, Raab, Matthew, Piel, Matthieu, Restuccia, Umberto, Matafora, Vittoria, Bachi, Angela, Barozzi, Sara, Parazzoli, Dario, Frittoli, Emanuela, Palamidessi, Andrea, Panciera, Tito, Piccolo, Stefano, Scita, Giorgio, Maiuri, Paolo, Havas, Kristina M., Zhou, Zhong-Wei, Kumar, Amit, Bartek, Jiri, Wang, Zhao-Qi, and Foiani, Marco

Published
2020
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9. Acetyl-CoA carboxylase 1 controls a lipid droplet–peroxisome axis and is a vulnerability of endocrine-resistant ER+ breast cancer.

Author

Bacci, Marina, Lorito, Nicla, Smiriglia, Alfredo, Subbiani, Angela, Bonechi, Francesca, Comito, Giuseppina, Morriset, Ludivine, El Botty, Rania, Benelli, Matteo, López-Velazco, Joanna I., Caffarel, Maria M., Urruticoechea, Ander, Sflomos, George, Malorni, Luca, Corsini, Michela, Ippolito, Luigi, Giannoni, Elisa, Meattini, Icro, Matafora, Vittoria, and Havas, Kristina

Subjects
ACETYL-CoA carboxylase, BREAST cancer, AROMATASE inhibitors, LIPIDS, TUMOR growth
Abstract

Targeting aromatase deprives ER+ breast cancers of estrogens and is an effective therapeutic approach for these tumors. However, drug resistance is an unmet clinical need. Lipidomic analysis of long-term estrogen-deprived (LTED) ER+ breast cancer cells, a model of aromatase inhibitor resistance, revealed enhanced intracellular lipid storage. Functional metabolic analysis showed that lipid droplets together with peroxisomes, which we showed to be enriched and active in the LTED cells, controlled redox homeostasis and conferred metabolic adaptability to the resistant tumors. This reprogramming was controlled by acetyl-CoA-carboxylase-1 (ACC1), whose targeting selectively impaired LTED survival. However, the addition of branched- and very long–chain fatty acids reverted ACC1 inhibition, a process that was mediated by peroxisome function and redox homeostasis. The therapeutic relevance of these findings was validated in aromatase inhibitor–treated patient-derived samples. Last, targeting ACC1 reduced tumor growth of resistant patient-derived xenografts, thus identifying a targetable hub to combat the acquisition of estrogen independence in ER+ breast cancers. Editor's summary: Aromatase inhibitors prevent estrogen production and can be effective against ER+ breast cancer, but subsequent tumor metabolic adaptation often thwarts treatment efficacy. Bacci et al. report that acetyl-CoA-carboxylase-1 (ACC1) promotes lipid mobilization in estrogen-deprived breast cancer cells, leading to anti-estrogen therapy resistance. Pharmacologically targeting ACC1 in patient-derived, treatment-resistant xenograft models reduced tumor growth and increased mouse survival. This work indicates that targeting ACC1 may be an avenue to resensitize ER+ breast cancer to endocrine-based therapies. —Catherine Charneski [ABSTRACT FROM AUTHOR]

Published
2024
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10. Supplementary Online Material from 3D-Informed Targeting of the Trop-2 Signal-Activation Site Drives Selective Cancer Vulnerability

Author

Guerra, Emanuela, primary, Trerotola, Marco, primary, Relli, Valeria, primary, Lattanzio, Rossano, primary, Tripaldi, Romina, primary, Ceci, Martina, primary, Boujnah, Khouloud, primary, Pantalone, Ludovica, primary, Sacchetti, Andrea, primary, Havas, Kristina M., primary, Simeone, Pasquale, primary, Travali, Nicole, primary, Querzoli, Patrizia, primary, Pedriali, Massimo, primary, Roversi, Pietro, primary, Iezzi, Manuela, primary, Tinari, Nicola, primary, Antolini, Laura, primary, and Alberti, Saverio, primary

Published
2023
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11. 3D-informed targeting of the Trop-2 signal-activation site drives selective cancer vulnerability

Author

Guerra, Emanuela, primary, Trerotola, Marco, additional, Relli, Valeria, additional, Lattanzio, Rossano, additional, Tripaldi, Romina, additional, Ceci, Martina, additional, Boujnah, Khouloud, additional, Pantalone, Ludovica, additional, Sacchetti, Andrea, additional, Havas, Kristina M., additional, Simeone, Pasquale, additional, Travali, Nicole, additional, Querzoli, Patrizia, additional, Pedriali, Massimo, additional, Roversi, Pietro, additional, Iezzi, Manuela, additional, Tinari, Nicola, additional, Antolini, Laura, additional, and Alberti, Saverio, additional

Published
2023
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12. Tissue fluidification promotes a cGAS–STING cytosolic DNA response in invasive breast cancer

Author

Frittoli, Emanuela, primary, Palamidessi, Andrea, additional, Iannelli, Fabio, additional, Zanardi, Federica, additional, Villa, Stefano, additional, Barzaghi, Leonardo, additional, Abdo, Hind, additional, Cancila, Valeria, additional, Beznoussenko, Galina V., additional, Della Chiara, Giulia, additional, Pagani, Massimiliano, additional, Malinverno, Chiara, additional, Bhattacharya, Dipanjan, additional, Pisati, Federica, additional, Yu, Weimiao, additional, Galimberti, Viviana, additional, Bonizzi, Giuseppina, additional, Martini, Emanuele, additional, Mironov, Alexander A., additional, Gioia, Ubaldo, additional, Ascione, Flora, additional, Li, Qingsen, additional, Havas, Kristina, additional, Magni, Serena, additional, Lavagnino, Zeno, additional, Pennacchio, Fabrizio Andrea, additional, Maiuri, Paolo, additional, Caponi, Silvia, additional, Mattarelli, Maurizio, additional, Martino, Sabata, additional, d’Adda di Fagagna, Fabrizio, additional, Rossi, Chiara, additional, Lucioni, Marco, additional, Tancredi, Richard, additional, Pedrazzoli, Paolo, additional, Vecchione, Andrea, additional, Petrini, Cristiano, additional, Ferrari, Francesco, additional, Lanzuolo, Chiara, additional, Bertalot, Giovanni, additional, Nader, Guilherme, additional, Foiani, Marco, additional, Piel, Matthieu, additional, Cerbino, Roberto, additional, Giavazzi, Fabio, additional, Tripodo, Claudio, additional, and Scita, Giorgio, additional

Published
2022
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13. PillarX: A Microfluidic Device to Profile Circulating Tumor Cell Clusters Based on Geometry, Deformability, and Epithelial State

Author

Green, Brenda J., primary, Marazzini, Margherita, additional, Hershey, Ben, additional, Fardin, Amir, additional, Li, Qingsen, additional, Wang, Zongjie, additional, Giangreco, Giovanni, additional, Pisati, Federica, additional, Marchesi, Stefano, additional, Disanza, Andrea, additional, Frittoli, Emanuela, additional, Martini, Emanuele, additional, Magni, Serena, additional, Beznoussenko, Galina V., additional, Vernieri, Claudio, additional, Lobefaro, Riccardo, additional, Parazzoli, Dario, additional, Maiuri, Paolo, additional, Havas, Kristina, additional, Labib, Mahmoud, additional, Sigismund, Sara, additional, Di Fiore, Pier Paolo, additional, Gunby, Rosalind H., additional, Kelley, Shana O., additional, and Scita, Giorgio, additional

Published
2022
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14. Metabolic shifts in residual breast cancer drive tumor recurrence

Author

Havas, Kristina M., Milchevskaya, Vladislava, Radic, Ksenija, Alladin, Ashna, Kafkia, Eleni, Garcia, Marta, Stolte, Jens, Klaus, Bernd, Rotmensz, Nicole, Gibson, Toby J., Burwinkel, Barbara, Schneeweiss, Andreas, Pruneri, Giancarlo, Patil, Kiran R., Sotillo, Rocio, and Jechlinger, Martin

Subjects
Mortality -- Risk factors, Recurrence (Disease) -- Complications and side effects, Breast cancer -- Complications and side effects, Health care industry
Abstract

Tumor recurrence is the leading cause of breast cancer-related death. Recurrences are largely driven by cancer cells that survive therapeutic intervention. This poorly understood population is referred to as minimal residual disease. Here, using mouse models that faithfully recapitulate human disease together with organoid cultures, we have demonstrated that residual cells acquire a transcriptionally distinct state from normal epithelium and primary tumors. Gene expression changes and functional characterization revealed altered lipid metabolism and elevated ROS as hallmarks of the cells that survive tumor regression. These residual cells exhibited increased oxidative DNA damage, potentiating the acquisition of somatic mutations during hormonal-induced expansion of the mammary cell population. Inhibition of either cellular fatty acid synthesis or fatty acid transport into mitochondria reduced cellular ROS levels and DNA damage, linking these features to lipid metabolism. Direct perturbation of these hallmarks in vivo, either by scavenging ROS or by halting the cyclic mammary cell population expansion, attenuated tumor recurrence. Finally, these observations were mirrored in transcriptomic and histological signatures of residual cancer cells from neoadjuvant-treated breast cancer patients. These results highlight the potential of lipid metabolism and ROS as therapeutic targets for reducing tumor recurrence in breast cancer patients., Introduction Despite advances in detection and therapy, breast cancer remains the second leading cause of cancer-related death in women. Mortality is largely due to tumor recurrence following initial therapeutic intervention [...]

Published
2017
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15. Tissue fluidification promotes a cGAS-STING cytosolic DNA response in invasive breast cancer

Author

Frittoli, Emanuela, Palamidessi, Andrea, Iannelli, Fabio, Zanardi, Federica, Villa, Stefano, Barzaghi, Leonardo, Abdo, Hind, Cancila, Valeria, Beznoussenko, Galina V, Della Chiara, Giulia, Pagani, Massimiliano, Malinverno, Chiara, Bhattacharya, Dipanjan, Pisati, Federica, Weimiao, Yu, Galimberti, Viviana, Bonizzi, Giuseppina, Martini, Emanuele, Mironov, Alexander A, Gioia, Ubaldo, Ascione, Floriana, Qingsen, Li, Havas, Kristina, Magni, Serena, Lavagnino, Zeno, Pennacchio, Fabrizio Andrea, Maiuri, Paolo, Caponi, Silvia, Mattarelli, Maurizio, Martino, Sabata, d'Adda di Fagagna, Fabrizio, Rossi, Chiara, Lucioni, Marco, Tancredi, Richard, Pedrazzoli, Paolo, Vecchione, Andrea, Petrini, Cristiano, Ferrari, Francesco, Lanzuolo, Chiara, Bertalot, Giovanni, Nader, Guilherme, Foiani, Marco, Piel, Matthieu, Cerbino, Roberto, Giavazzi, Fabio, Tripodo, Claudio, Scita, Giorgio, Frittoli, Emanuela, Palamidessi, Andrea, Iannelli, Fabio, Zanardi, Federica, Villa, Stefano, Barzaghi, Leonardo, Abdo, Hind, Cancila, Valeria, Beznoussenko, Galina V, Della Chiara, Giulia, Pagani, Massimiliano, Malinverno, Chiara, Bhattacharya, Dipanjan, Pisati, Federica, Yu, Weimiao, Galimberti, Viviana, Bonizzi, Giuseppina, Martini, Emanuele, Mironov, Alexander A, Gioia, Ubaldo, Ascione, Floriana, Li, Qingsen, Havas, Kristina, Magni, Serena, Lavagnino, Zeno, Pennacchio, Fabrizio Andrea, Maiuri, Paolo, Caponi, Silvia, Mattarelli, Maurizio, Martino, Sabata, d'Adda di Fagagna, Fabrizio, Rossi, Chiara, Lucioni, Marco, Tancredi, Richard, Pedrazzoli, Paolo, Vecchione, Andrea, Petrini, Cristiano, Ferrari, Francesco, Lanzuolo, Chiara, Bertalot, Giovanni, Nader, Guilherme, Foiani, Marco, Piel, Matthieu, Cerbino, Roberto, Giavazzi, Fabio, Tripodo, Claudio, and Scita, Giorgio

Subjects
C-gas, invasive breast cancer, DNA response, breast cancer, cGAS-STING, Settore MED/05 - Patologia Clinica, biochemical mechanotransduction, DNA, Settore MED/08 - Anatomia Patologica, cGAS-STING (cyclic GMP-AMP synthase-signalling
Abstract

The process in which locally confined epithelial malignancies progressively evolve into invasive cancers is often promoted by unjamming, a phase transition from a solid-like to a liquid-like state, which occurs in various tissues. Whether this tissue-level mechanical transition impacts phenotypes during carcinoma progression remains unclear. Here we report that the large fluctuations in cell density that accompany unjamming result in repeated mechanical deformations of cells and nuclei. This triggers a cellular mechano-protective mechanism involving an increase in nuclear size and rigidity, heterochromatin redistribution and remodelling of the perinuclear actin architecture into actin rings. The chronic strains and stresses associated with unjamming together with the reduction of Lamin B1 levels eventually result in DNA damage and nuclear envelope ruptures, with the release of cytosolic DNA that activates a cGAS-STING (cyclic GMP-AMP synthase-signalling adaptor stimulator of interferon genes)-dependent cytosolic DNA response gene program. This mechanically driven transcriptional rewiring ultimately alters the cell state, with the emergence of malignant traits, including epithelial-to-mesenchymal plasticity phenotypes and chemoresistance in invasive breast carcinoma.

Published
2021

17. Trop-2, Na+/K+ATPase, CD9, PKCα, cofilin assemble a membrane signaling super-complex that drives colorectal cancer growth and invasion

Author

Guerra, Emanuela, Relli, Valeria, Ceci, Martina, Tripaldi, Romina, Simeone, Pasquale, Aloisi, Anna Laura, Pantalone, Ludovica, La Sorda, Rossana, Lattanzio, Rossano, Sacchetti, Andrea, Havas, Kristina, Guarnieri, Simone, Vergara, Daniele, Fournier, Isabelle, Salzet, Michel, Tinari, Nicola, Piantelli, Mauro, Trerotola, Marco, and Alberti, Saverio

Abstract

Trop-2 is a transmembrane signal transducer that is overexpressed in most human cancers, and drives malignant progression. To gain knowledge on the higher-order molecular mechanisms that drive Trop-2 signaling, we applied next-generation sequencing, proteomics, and high-resolution microscopy to models and primary cases of human colorectal cancer (CRC). We had previously shown that Trop-2 induces a Ca2+signal. We reveal here that Trop-2 binds the cell membrane Na+/K+-ATPase, and that clustering of Trop-2 induces an intracellular Ca2+rise followed by membrane translocation of PKCα, which in turn phosphorylates the Trop-2 cytoplasmic tail. This feed-forward signaling is promoted by the binding of Trop-2 to the PKCα membrane-anchor CD9. CRISPR-based inactivation of CD9in CRC cells shows that CD9 is required by Trop-2 for recruiting PKCα and cofilin-1 to the cell membrane. This induces malignant progression through proteolytic cleavage of E-cadherin, remodeling of the β-actin cytoskeleton, and activation of Akt and ERK. The interaction between Trop-2 and CD9 was validated in vivo in murine models of CRC growth and invasion. Overexpression of the components of this Trop-2-driven super-complex significantly worsened disease-free and overall survival of CRC patients, supporting a pivotal relevance in CRC malignant progression. Our findings demonstrate a previously unsuspected layer of cancer growth regulation, which is dormant in normal tissues, and is activated by Trop-2 in cancer cells.

Published
2022
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19. Abstract 367: Trop-2 activates a dormant Na+/K+-ATPase/PKCα/CD9/ezrin signaling axis to override the basal growth program of cancer cells

Author

Trerotola, Marco, primary, Relli, Valeria, additional, Tripaldi, Romina, additional, Sacchetti, Andrea, additional, Havas, Kristina, additional, Simeone, Pasquale, additional, Guerra, Emanuela, additional, Aloisi, Annalaura, additional, Sorda, Rossana La, additional, Lattanzio, Rossano, additional, Vergara, Daniele, additional, Fournier, Isabelle, additional, Salzet, Michel, additional, Piantelli, Mauro, additional, and Alberti, Saverio, additional

Published
2017
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20. Acetyl-CoA carboxylase 1 controls a lipid droplet–peroxisome axis and is a vulnerability of endocrine-resistant ER+breast cancer

Author

Bacci, Marina, Lorito, Nicla, Smiriglia, Alfredo, Subbiani, Angela, Bonechi, Francesca, Comito, Giuseppina, Morriset, Ludivine, El Botty, Rania, Benelli, Matteo, López-Velazco, Joanna I., Caffarel, Maria M., Urruticoechea, Ander, Sflomos, George, Malorni, Luca, Corsini, Michela, Ippolito, Luigi, Giannoni, Elisa, Meattini, Icro, Matafora, Vittoria, Havas, Kristina, Bachi, Angela, Chiarugi, Paola, Marangoni, Elisabetta, and Morandi, Andrea

Abstract

Targeting aromatase deprives ER+breast cancers of estrogens and is an effective therapeutic approach for these tumors. However, drug resistance is an unmet clinical need. Lipidomic analysis of long-term estrogen-deprived (LTED) ER+breast cancer cells, a model of aromatase inhibitor resistance, revealed enhanced intracellular lipid storage. Functional metabolic analysis showed that lipid droplets together with peroxisomes, which we showed to be enriched and active in the LTED cells, controlled redox homeostasis and conferred metabolic adaptability to the resistant tumors. This reprogramming was controlled by acetyl-CoA-carboxylase-1 (ACC1), whose targeting selectively impaired LTED survival. However, the addition of branched- and very long–chain fatty acids reverted ACC1 inhibition, a process that was mediated by peroxisome function and redox homeostasis. The therapeutic relevance of these findings was validated in aromatase inhibitor–treated patient-derived samples. Last, targeting ACC1 reduced tumor growth of resistant patient-derived xenografts, thus identifying a targetable hub to combat the acquisition of estrogen independence in ER+breast cancers.

Published
2024
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21. Lipid Droplets Define a Sub-Population of Breast Cancer Stem Cells.

Author

Hershey, Benjamin J., Vazzana, Roberta, Joppi, Débora L., and Havas, Kristina M.

Subjects
CANCER stem cells, BREAST cancer, PERILIPIN, LIPID metabolism, CYTOLOGY
Abstract

Tumor recurrence is now the leading cause of breast cancer-related death. These recurrences are believed to arise from residual cancer stem cells that survive initial therapeutic intervention. Therefore, a comprehensive understanding of cancer stem cell biology is needed to generate more effective therapies. Here we investigate the association between dysregulation of lipid metabolism and breast cancer stem cells. Focusing specifically on lipid droplets, we found that the lipid droplet number correlates with stemness in a panel of breast cell lines. Using a flow cytometry-based method developed for this study, we establish a means to isolate cells with augmented lipid droplet loads from total populations and show that they are enriched in cancer stem cells. Furthermore, pharmacological targeting of fatty acid metabolism reveals a metabolic addiction in a subset of cell lines. Our results highlight a key role for the lipid metabolism in the maintenance of the breast cancer stem cell pool, and as such, suggest it as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Published
2020
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