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The autophagic tumor stroma model of cancer

Role of oxidative stress and ketone production in fueling tumor cell metabolism

, , , , , , , , , , , , & show all
Pages 3485-3505 | Published online: 01 Sep 2010

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Pin Fu, Fuchun Chen, Qi Pan, Xianda Zhao, Chen Zhao, William Chi-Shing Cho & Honglei Chen. (2017) The different functions and clinical significances of caveolin-1 in human adenocarcinoma and squamous cell carcinoma. OncoTargets and Therapy 10, pages 819-835.
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Subhadip Mukhopadhyay, Niharika Sinha, Durgesh Nandini Das, Prashanta Kumar Panda, Prajna Paramita Naik & Sujit Kumar Bhutia. (2016) Clinical relevance of autophagic therapy in cancer: Investigating the current trends, challenges, and future prospects. Critical Reviews in Clinical Laboratory Sciences 53:4, pages 228-252.
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Pia Hönscheid, Kaustubh Datta & Michael H. Muders. (2014) Autophagy: Detection, regulation and its role in cancer and therapy response. International Journal of Radiation Biology 90:8, pages 628-635.
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Haiqi Lu, Guangliang Li, Leiming Liu, Lifeng Feng, Xian Wang & Hongchuan Jin. (2013) Regulation and function of mitophagy in development and cancer. Autophagy 9:11, pages 1720-1736.
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Michael P. Lisanti, Ubaldo E. Martinez-Outschoorn & Federica Sotgia. (2013) Oncogenes induce the cancer-associated fibroblast phenotype: Metabolic symbiosis and “fibroblast addiction” are new therapeutic targets for drug discovery. Cell Cycle 12:17, pages 2723-2732.
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Ubaldo E Martinez-Outschoorn, Joseph M Curry, Ying-Hui Ko, Zhao Lin, Madalina Tuluc, David Cognetti, Ruth C Birbe, Edmund Pribitkin, Alessandro Bombonati, Richard G Pestell, Anthony Howell, Federica Sotgia & Michael P Lisanti. (2013) Oncogenes and inflammation rewire host energy metabolism in the tumor microenvironment. Cell Cycle 12:16, pages 2580-2597.
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Jun-Lin Guan, Anna Katharina Simon, Mark Prescott, Javier A. Menendez, Fei Liu, Fen Wang, Chenran Wang, Ernst Wolvetang, Alejandro Vazquez-Martin & Jue Zhang. (2013) Autophagy in stem cells. Autophagy 9:6, pages 830-849.
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Paola Avena, Wanda Anselmo, Chenguang Wang, Richard G. Pestell, Rebecca S. Lamb, Ivan Casaburi, Sebastiano Andò, Ubaldo E. Martinez-Outschoorn & Michael P. Lisanti. (2013) Compartment-specific activation of PPARγ governs breast cancer tumor growth, via metabolic reprogramming and symbiosis. Cell Cycle 12:9, pages 1360-1370.
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Haiyan Zhai, Andrew Fesler & Jingfang Ju. (2013) MicroRNA. Cell Cycle 12:2, pages 246-250.
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Rosa Sanchez-Alvarez, Ubaldo E. Martinez-Outschoorn, Zhao Lin, Rebecca Lamb, James Hulit, Anthony Howell, Federica Sotgia, Emanuel Rubin & Michael P. Lisanti. (2013) Ethanol exposure induces the cancer-associated fibroblast phenotype and lethal tumor metabolism. Cell Cycle 12:2, pages 289-301.
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William H. Chappell, Stephen L. Abrams, Richard A. Franklin, Michelle M. LaHair, Giuseppe Montalto, Melchiorre Cervello, Alberto M. Martelli, Ferdinando Nicoletti, Saverio Candido, Massimo Libra, Jerry Polesel, Renato Talamini, Michele Milella, Agostino Tafuri, Linda S. Steelman & James A. McCubrey. (2012) Ectopic NGAL expression can alter sensitivity of breast cancer cells to EGFR, Bcl-2, CaM-K inhibitors and the plant natural product berberine. Cell Cycle 11:23, pages 4447-4461.
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Ubaldo E. Martinez-Outschoorn, Zhao Lin, Diana Whitaker-Menezes, Anthony Howell, Michael P. Lisanti & Federica Sotgia. (2012) Ketone bodies and two-compartment tumor metabolism: Stromal ketone production fuels mitochondrial biogenesis in epithelial cancer cells. Cell Cycle 11:21, pages 3956-3963.
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Claudia Capparelli, Barbara Chiavarina, Diana Whitaker-Menezes, Timothy G. Pestell, Richard G. Pestell, James Hulit, Sebastiano Andò, Anthony Howell, Ubaldo E. Martinez-Outschoorn, Federica Sotgia & Michael P. Lisanti. (2012) CDK inhibitors (p16/p19/p21) induce senescence and autophagy in cancer-associated fibroblasts, “fueling” tumor growth via paracrine interactions, without an increase in neo-angiogenesis. Cell Cycle 11:19, pages 3599-3610.
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Carmela Guido, Diana Whitaker-Menezes, Claudia Capparelli, Renee Balliet, Zhao Lin, Richard G. Pestell, Anthony Howell, Saveria Aquila, Sebastiano Andò, Ubaldo Martinez-Outschoorn, Federica Sotgia & Michael P. Lisanti. (2012) Metabolic reprogramming of cancer-associated fibroblasts by TGF-β drives tumor growth: Connecting TGF-β signaling with “Warburg-like” cancer metabolism and L-lactate production. Cell Cycle 11:16, pages 3019-3035.
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Claudia Capparelli, Carmela Guido, Diana Whitaker-Menezes, Gloria Bonuccelli, Renee Balliet, Timothy G. Pestell, Allison F. Goldberg, Richard G. Pestell, Anthony Howell, Sharon Sneddon, Ruth Birbe, Aristotelis Tsirigos, Ubaldo Martinez-Outschoorn, Federica Sotgia & Michael P. Lisanti. (2012) Autophagy and senescence in cancer-associated fibroblasts metabolically supports tumor growth and metastasis, via glycolysis and ketone production. Cell Cycle 11:12, pages 2285-2302.
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Federica Sotgia, Diana Whitaker-Menezes, Ubaldo E. Martinez-Outschoorn, Neal Flomenberg, Ruth Birbe, Agnieszka K. Witkiewicz, Anthony Howell, Nancy J. Philp, Richard G. Pestell & Michael P. Lisanti. (2012) Mitochondrial metabolism in cancer metastasis. Cell Cycle 11:7, pages 1445-1454.
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Agnieszka K. Witkiewicz, Diana Whitaker-Menezes, Abhijit Dasgupta, Nancy J. Philp, Zhao Lin, Ricardo Gandara, Sharon Sneddon, Ubaldo E. Martinez-Outschoorn, Federica Sotgia & Michael P. Lisanti. (2012) Using the “reverse Warburg effect” to identify high-risk breast cancer patients. Cell Cycle 11:6, pages 1108-1117.
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Adam Ertel, Aristotelis Tsirigos, Diana Whitaker-Menezes, Ruth Birbe, Stephanos Pavlides, Ubaldo E. Martinez-Outschoorn, Richard G. Pestell, Anthony Howell, Federica Sotgia & Michael P. Lisanti. (2012) Is cancer a metabolic rebellion against host aging? In the quest for immortality, tumor cells try to save themselves by boosting mitochondrial metabolism. Cell Cycle 11:2, pages 253-263.
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Ubaldo E. Martinez-Outschoorn, Richard G. Pestell, Anthony Howell, Mark L. Tykocinski, Fnu Nagajyothi, Fabiana S. Machado, Herbert B. Tanowitz, Federica Sotgia & Michael P. Lisanti. (2011) Energy transfer in "parasitic" cancer metabolism. Cell Cycle 10:24, pages 4208-4216.
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Barbara Chiavarina , Diana Whitaker-Menezes, Ubaldo E. Martinez-Outschoorn, Agnieszka K. Witkiewicz, Ruth Birbe, Anthony Howell, Richard G. Pestell, Johanna Smith, Rene Daniel, Federica Sotgia & Michael P. Lisanti. (2011) Pyruvate kinase expression (PKM1 and PKM2) in cancer-associated fibroblasts drives stromal nutrient production and tumor growth. Cancer Biology & Therapy 12:12, pages 1101-1113.
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Ying-Hui Ko, Zhao Lin, Neal Flomenberg, Richard G. Pestell, Anthony Howell, Federica Sotgia, Michael P. Lisanti & Ubaldo E. Martinez-Outschoorn. (2011) Glutamine fuels a vicious cycle of autophagy in the tumor stroma and oxidative mitochondrial metabolism in epithelial cancer cells. Cancer Biology & Therapy 12:12, pages 1085-1097.
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Renee M. Balliet, Claudia Capparelli, Carmela Guido, Timothy G. Pestell, Ubaldo E. Martinez-Outschoorn, Zhao Lin, Diana Whitaker-Menezes, Barbara Chiavarina, Richard G. Pestell, Anthony Howell, Federica Sotgia & Michael P. Lisanti. (2011) Mitochondrial oxidative stress in cancer-associated fibroblasts drives lactate production, promoting breast cancer tumor growth. Cell Cycle 10:23, pages 4065-4073.
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Diana Whitaker-Menezes, Ubaldo E. Martinez-Outschoorn, Neal Flomenberg, Ruth Birbe, Agnieszka K. Witkiewicz, Anthony Howell, Stephanos Pavlides, Aristotelis Tsirigos, Adam Ertel, Richard G. Pestell, Paolo Broda, Carlo Minetti, Michael P. Lisanti & Federica Sotgia. (2011) Hyperactivation of oxidative mitochondrial metabolism in epithelial cancer cells in situ. Cell Cycle 10:23, pages 4047-4064.
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Ubaldo E. Martinez-Outschoorn, Allison F. Goldberg, Zhao Lin, Ying-Hui Ko, Neal Flomenberg, Chenguang Wang, Stephanos Pavlides, Richard G. Pestell, Anthony Howell, Federica Sotgia & Michael P. Lisanti. (2011) Anti-estrogen resistance in breast cancer is induced by the tumor microenvironment and can be overcome by inhibiting mitochondrial function in epithelial cancer cells. Cancer Biology & Therapy 12:10, pages 924-938.
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Marco Muda. (2011) DUSPs strike again. Cell Cycle 10:17, pages 2827-2835.
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Michael P Lisanti, Ubaldo E. Martinez-Outschoorn, Zhao Lin, Stephanos Pavlides, Diana Whitaker-Menezes, Richard G. Pestell, Anthony Howell & Federica Sotgia. (2011) Hydrogen peroxide fuels aging, inflammation, cancer metabolism and metastasis. Cell Cycle 10:15, pages 2440-2449.
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Ubaldo E. Martinez-Outschoorn, Zhao Lin , Casey Trimmer, Neal Flomenberg, Chenguang Wang, Stephanos Pavlides, Richard G. Pestell, Anthony Howell, Federica Sotgia & Michael P Lisanti. (2011) Cancer cells metabolically "fertilize" the tumor microenvironment with hydrogen peroxide, driving the Warburg effect. Cell Cycle 10:15, pages 2504-2520.
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Michael P Lisanti, Ubaldo E. Martinez-Outschoorn, Stephanos Pavlides, Diana Whitaker-Menezes, Richard G. Pestell, Anthony Howell & Federica Sotgia. (2011) Accelerated aging in the tumor microenvironment. Cell Cycle 10:13, pages 2059-2063.
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Remedios Castello-Cros, Diana Whitaker-Menezes, Alex Molchansky, George Purkins, Louis J. Soslowsky, David P. Beason, Federica Sotgia, Renato V. Iozzo & Michael P Lisanti. (2011) Scleroderma-like properties of skin from caveolin-1-deficient mice. Cell Cycle 10:13, pages 2140-2150.
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Remedios Castello-Cros, Gloria Bonnuccelli, Alex Molchansky, Franco Capozza, Agnieszka K. Witkiewicz, Ruth Birbe, Anthony Howell, Richard G. Pestell, Diana Whitaker-Menezes, Federica Sotgia & Michael P Lisanti. (2011) Matrix remodeling stimulates stromal autophagy, “fueling” cancer cell mitochondrial metabolism and metastasis. Cell Cycle 10:12, pages 2021-2034.
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Agnieszka K. Witkiewicz, Jessica Kline, Maria Queenan, Jonathan R. Brody, Aristotelis Tsirigos, Erhan Bilal, Stephanos Pavlides, Adam Ertel, Federica Sotgia & Michael P Lisanti. (2011) Molecular profiling of a lethal tumor microenvironment, as defined by stromal caveolin-1 status in breast cancers. Cell Cycle 10:11, pages 1794-1809.
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Ubaldo E. Martinez-Outschoorn, Diana Whitaker-Menezes, Zhao Lin, Neal Flomenberg, Anthony Howell, Richard G. Pestell, Michael P Lisanti & Federica Sotgia. (2011) Cytokine production and inflammation drive autophagy in the tumor microenvironment. Cell Cycle 10:11, pages 1784-1793.
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Diana Whitaker-Menezes, Ubaldo E. Martinez-Outschoorn, Zhao Lin, Adam Ertel, Neal Flomenberg, Agnieszka K. Witkiewicz, Ruth Birbe, Anthony Howell, Stephanos Pavlides, Ricardo Gandara, Richard G. Pestell, Federica Sotgia, Nancy J. Philp & Michael P Lisanti. (2011) Evidence for a stromal-epithelial “lactate shuttle” in human tumors. Cell Cycle 10:11, pages 1772-1783.
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Ubaldo E. Martinez-Outschoorn, Marco Prisco, Adam Ertel, Aristotelis Tsirigos, Zhao Lin, Stephanos Pavlides, Chengwang Wang, Neal Flomenberg, Erik S. Knudsen, Anthony Howell, Richard G. Pestell, Federica Sotgia & Michael P Lisanti. (2011) Ketones and lactate increase cancer cell “stemness,” driving recurrence, metastasis and poor clinical outcome in breast cancer. Cell Cycle 10:8, pages 1271-1286.
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Casey Trimmer, Federica Sotgia, Diana Whitaker-Menezes, Renee M. Balliet, Gregory Eaton, Ubaldo E. Martinez-Outschoorn, Stephanos Pavlides, Anthony Howell, Renato V. Iozzo, Richard G. Pestell, Philipp E. Scherer, Franco Capozza & Michael P. Lisanti. (2011) Caveolin-1 and mitochondrial SOD2 (MnSOD) function as tumor suppressors in the stromal microenvironment. Cancer Biology & Therapy 11:4, pages 383-394.
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John Stingl & Robert B Clarke. (2011) Hormones and cancer: update from Tokyo 2010. Expert Review of Endocrinology & Metabolism 6:1, pages 31-33.
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Ubaldo E. Martinez-Outschoorn, Diana Whitaker-Menezes, Stephanos Pavlides, Barbara Chiavarina, Gloria Bonuccelli, Casey Trimmer, Aristotelis Tsirigos, Gemma Migneco, Agnieszka K. Witkiewicz, Renee M. Balliet, Isabelle Mercier, Chengwang Wang, Neal Flomenberg, Anthony Howell, Zhao Lin, Jaime Caro, Richard G. Pestell, Federica Sotgia & Michael P Lisanti. (2010) The autophagic tumor stroma model of cancer or “battery-operated tumor growth”. Cell Cycle 9:21, pages 4297-4306.
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Olga Aprelikova, Xiang Yu, John Palla, Bih-Rong Wei, Simone John, Ming Yi, Robert Stephens, R. Mark Simpson, John I. Risinger, Amir Jazaeri & John Niederhuber. (2010) The role of miR-31 and its target gene SATB2 in cancer-associated fibroblasts. Cell Cycle 9:21, pages 4387-4398.
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Michael P. Lisanti, Ubaldo E. Martinez-Outschoorn, Barbara Chiavarina, Stephanos Pavlides, Diana Whitaker-Menezes, Aristotelis Tsirigos, Agnieszka K. Witkiewicz, Zhao Lin, Renee M. Balliet, Anthony Howell & Federica Sotgia. (2010) Understanding the "lethal" drivers of tumor-stroma co-evolution. Cancer Biology & Therapy 10:6, pages 537-542.
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Ubaldo E. Martinez-Outschoorn, Casey Trimmer, Zhao Lin, Diana Whitaker-Menezes , Barbara Chiavarina, Jie Zhou, Chenguang Wang, Stephanos Pavlides, Maria P. Martinez-Cantarin, Franco Capozza, Agnieszka K. Witkiewicz, Neal Flomenberg, Anthony Howell, Richard G. Pestell, Jaime Caro, Michael P. Lisanti & Federica Sotgia. (2010) Autophagy in cancer associated fibroblasts promotes tumor cell survival. Cell Cycle 9:17, pages 3515-3533.
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Barbara Chiavarina, Diana Whitaker-Menezes, Gemma Migneco, Ubaldo E. Martinez-Outschoorn, Stephanos Pavlides, Anthony Howell, Herbert B. Tanowitz, Mathew C. Casimiro, Chenguang Wang, Richard G. Pestell, Philip Grieshaber, Jaime Caro, Federica Sotgia & Michael P. Lisanti. (2010) HIF1-alpha functions as a tumor promoter in cancer-associated fibroblasts, and as a tumor suppressor in breast cancer cells. Cell Cycle 9:17, pages 3534-3551.
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Gloria Bonuccelli, Aristotelis Tsirigos, Diana Whitaker-Menezes, Stephanos Pavlides, Richard G. Pestell, Barbara Chiavarina, Philippe G. Frank, Neal Flomenberg, Anthony Howell, Ubaldo E. Martinez-Outschoorn, Federica Sotgia & Michael P. Lisanti. (2010) Ketones and lactate “fuel” tumor growth and metastasis. Cell Cycle 9:17, pages 3506-3514.
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