Exploring metabolic reprogramming in melanoma via acquired resistance to the oxidative phosphorylation inhibitor phenformin.
Journal
Melanoma research
ISSN: 1473-5636
Titre abrégé: Melanoma Res
Pays: England
ID NLM: 9109623
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
pubmed:
23
5
2019
medline:
18
12
2020
entrez:
23
5
2019
Statut:
ppublish
Résumé
Therapeutic failures in cancer therapy are often associated with metabolic plasticity. The use of metabolic modulators as anti-cancer agents has been effective in correcting metabolic alterations; however, molecular events behind metabolic switch are still largely unexplored. Herein, we characterize the molecular and functional events that follow prolonged oxidative phosphorylation inhibition by phenformin in order to study how melanoma cells adapt to this specific metabolic pressure. We show that melanoma cells cultured up to 3 months with high doses of phenformin (R-cells) are less viable and migrate and invade less than parental (S-) cells. Microarray analysis of R-melanoma cells reveals a switch in the energy production strategy accompanied by the modulation of several immunological-associated genes. R-cells display low oxygen consumption rate and high basal extracellular acidification rate. When treated with vemurafenib, R-cell viability, growth and extracellular signal-regulated kinase activation decrease. Finally, phenformin withdrawal reverts R-cells phenotype. In summary, our study provides an in vitro model of on-off metabolic switch in melanoma and reveals interesting molecular signatures controlling metabolic reprogramming in this tumour.
Identifiants
pubmed: 31116160
doi: 10.1097/CMR.0000000000000624
pii: 00008390-202002000-00001
doi:
Substances chimiques
Hypoglycemic Agents
0
Phenformin
DD5K7529CE
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-13Références
Ascierto PA. Editorial: Combination strategies in the treatment of melanoma. Front Oncol. 2016; 6:67
Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell. 2017; 168:707–723
Morandi A, Indraccolo S. Linking metabolic reprogramming to therapy resistance in cancer. Biochim Biophys Acta Rev Cancer. 2017; 1868:1–6
McArthur GA. Combination therapies to inhibit the RAF/MEK/ERK pathway in melanoma: we are not done yet. Front Oncol. 2015; 5:161
Gopal YN, Rizos H, Chen G, Deng W, Frederick DT, Cooper ZA, et al. Inhibition of mtorc1/2 overcomes resistance to MAPK pathway inhibitors mediated by PGC1α and oxidative phosphorylation in melanoma. Cancer Res. 2014; 74:7037–7047
Kaplon J, Zheng L, Meissl K, Chaneton B, Selivanov VA, Mackay G, et al. A key role for mitochondrial gatekeeper pyruvate dehydrogenase in oncogene-induced senescence. Nature. 2013; 498:109–112
Ward PS, Thompson CB. Metabolic reprogramming: a cancer hallmark even warburg did not anticipate. Cancer Cell. 2012; 21:297–308
Ben Sahra I, Le Marchand-Brustel Y, Tanti JF, Bost F. Metformin in cancer therapy: a new perspective for an old antidiabetic drug? Mol Cancer Ther. 2010; 9:1092–1099
Orecchioni S, Reggiani F, Talarico G, Mancuso P, Calleri A, Gregato G, et al. The biguanides metformin and phenformin inhibit angiogenesis, local and metastatic growth of breast cancer by targeting both neoplastic and microenvironment cells. Int J Cancer. 2015; 136:E534–E544
Yuan P, Ito K, Perez-Lorenzo R, Del Guzzo C, Lee JH, Shen CH, et al. Phenformin enhances the therapeutic benefit of BRAF(V600E) inhibition in melanoma. Proc Natl Acad Sci U S A. 2013; 110:18226–18231
Trousil S, Chen S, Mu C, Shaw FM, Yao Z, Ran Y, et al. Phenformin enhances the efficacy of ERK inhibition in NF1-mutant melanoma. J Invest Dermatol. 2017; 137:1135–1143
Talarico G, Orecchioni S, Dallaglio K, Reggiani F, Mancuso P, Calleri A, et al. Aspirin and atenolol enhance metformin activity against breast cancer by targeting both neoplastic and microenvironment cells. Sci Rep. 2016; 6:18673
Petti C, Vegetti C, Molla A, Bersani I, Cleris L, Mustard KJ, et al. AMPK activators inhibit the proliferation of human melanomas bearing the activated MAPK pathway. Melanoma Res. 2012; 22:341–350
Petrachi T, Romagnani A, Albini A, Longo C, Argenziano G, Grisendi G, et al. Therapeutic potential of the metabolic modulator phenformin in targeting the stem cell compartment in melanoma. Oncotarget. 2017; 8:6914–6928
Haq R, Fisher DE, Widlund HR. Molecular pathways: BRAF induces bioenergetic adaptation by attenuating oxidative phosphorylation. Clin Cancer Res. 2014; 20:2257–2263
Luo Y, Dallaglio K, Chen Y, Robinson WA, Robinson SE, McCarter MD, et al. ALDH1A isozymes are markers of human melanoma stem cells and potential therapeutic targets. Stem Cells. 2012; 30:2100–2113
Pfeiffer T, Schuster S, Bonhoeffer S. Cooperation and competition in the evolution of ATP-producing pathways. Science. 2001; 292:504–507
Zhang G, Frederick DT, Wu L, Wei Z, Krepler C, Srinivasan S, et al. Targeting mitochondrial biogenesis to overcome drug resistance to MAPK inhibitors. J Clin Invest. 2016; 126:1834–1856
Navarro P, Bueno MJ, Zagorac I, Mondejar T, Sanchez J, Mourón S, et al. Targeting tumor mitochondrial metabolism overcomes resistance to antiangiogenics. Cell Rep. 2016; 15:2705–2718
Livingstone E, Swann S, Lilla C, Schadendorf D, Roesch A. Combining BRAF(V) (600E) inhibition with modulators of the mitochondrial bioenergy metabolism to overcome drug resistance in metastatic melanoma. Exp Dermatol. 2015; 24:709–710
Peppicelli S, Bianchini F, Calorini L. Metabolic reprogramming as a continuous changing behavior of tumor cells. Tumour Biol. 2015; 36:5759–5762
Peppicelli S, Toti A, Giannoni E, Bianchini F, Margheri F, Del Rosso M, Calorini L. Metformin is also effective on lactic acidosis-exposed melanoma cells switched to oxidative phosphorylation. Cell Cycle. 2016; 15:1908–1918
Albini A, Bassani B, Baci D, Dallaglio K, Gallazzi M, Corradino P, et al. Nutraceuticals and “repurposed” drugs of phytochemical origin in prevention and interception of chronic degenerative disease and cancer. Curr Med Chem. 2019; 26:973–987
Rajeshkumar NV, Yabuuchi S, Pai SG, De Oliveira E, Kamphorst JJ, Rabinowitz JD, et al. Treatment of pancreatic cancer patient-derived xenograft panel with metabolic inhibitors reveals efficacy of phenformin. Clin Cancer Res. 2017; 23:5639–5647
Gravel SP, Hulea L, Toban N, Birman E, Blouin MJ, Zakikhani M, et al. Serine deprivation enhances antineoplastic activity of biguanides. Cancer Res. 2014; 74:7521–7533
Kim SH, Li M, Trousil S, Zhang Y, Pasca di Magliano M, Swanson KD, Zheng B. Phenformin inhibits myeloid-derived suppressor cells and enhances the anti-tumor activity of PD-1 blockade in melanoma. J Invest Dermatol. 2017; 137:1740–1748
Vazquez-Martin A, Oliveras-Ferraros C, Del Barco S, Martin-Castillo B, Menendez JA. If mammalian target of metformin indirectly is mammalian target of rapamycin, then the insulin-like growth factor-1 receptor axis will audit the efficacy of metformin in cancer clinical trials. J Clin Oncol. 2009; 27:e207–e209; author reply e210
Menendez JA, Cufí S, Oliveras-Ferraros C, Martin-Castillo B, Joven J, Vellon L, Vazquez-Martin A. Metformin and the ATM DNA damage response (DDR): accelerating the onset of stress-induced senescence to boost protection against cancer. Aging (Albany NY). 2011; 3:1063–1077
Leucci E, Vendramin R, Spinazzi M, Laurette P, Fiers M, Wouters J, et al. Melanoma addiction to the long non-coding RNA SAMMSON. Nature. 2016; 531:518–522
Cantó C, Auwerx J. AMP-activated protein kinase and its downstream transcriptional pathways. Cell Mol Life Sci. 2010; 67:3407–3423
Giordano C, Iommarini L, Giordano L, Maresca A, Pisano A, Valentino ML, et al. Efficient mitochondrial biogenesis drives incomplete penetrance in leber’s hereditary optic neuropathy. Brain. 2014; 137:335–353
Oliveras-Ferraros C, Vazquez-Martin A, Cuyàs E, Corominas-Faja B, Rodríguez-Gallego E, Fernández-Arroyo S, et al. Acquired resistance to metformin in breast cancer cells triggers transcriptome reprogramming toward a degradome-related metastatic stem-like profile. Cell Cycle. 2014; 13:1132–1144
Roesch A, Fukunaga-Kalabis M, Schmidt EC, Zabierowski SE, Brafford PA, Vultur A, et al. A temporarily distinct subpopulation of slow-cycling melanoma cells is required for continuous tumor growth. Cell. 2010; 141:583–594
Scherbakov AM, Sorokin DV, Tatarskiy VV Jr, Prokhorov NS, Semina SE, Berstein LM, Krasil’nikov MA. The phenomenon of acquired resistance to metformin in breast cancer cells: the interaction of growth pathways and estrogen receptor signaling. IUBMB Life. 2016; 68:281–292
Ruzzolini J, Peppicelli S, Andreucci E, Bianchini F, Margheri F, Laurenzana A, et al. Everolimus selectively targets vemurafenib resistant BRAFV600E melanoma cells adapted to low ph. Cancer Lett. 2017; 408:43–54
Baenke F, Chaneton B, Smith M, Van Den Broek N, Hogan K, Tang H, et al. Resistance to BRAF inhibitors induces glutamine dependency in melanoma cells. Mol Oncol. 2016; 10:73–84
Nicklin P, Bergman P, Zhang B, Triantafellow E, Wang H, Nyfeler B, et al. Bidirectional transport of amino acids regulates mtor and autophagy. Cell. 2009; 136:521–534
Yang C, Sudderth J, Dang T, Bachoo RM, Bachoo RG, McDonald JG, DeBerardinis RJ. Glioblastoma cells require glutamate dehydrogenase to survive impairments of glucose metabolism or akt signaling. Cancer Res. 2009; 69:7986–7993
Dinarello CA, Nold-Petry C, Nold M, Fujita M, Li S, Kim S, Bufler P. Suppression of innate inflammation and immunity by interleukin-37. Eur J Immunol. 2016; 46:1067–1081
Cavalli G, Justice JN, Boyle KE, D’Alessandro A, Eisenmesser EZ, Herrera JJ, et al. Interleukin 37 reverses the metabolic cost of inflammation, increases oxidative respiration, and improves exercise tolerance. Proc Natl Acad Sci U S A. 2017; 114:2313–2318
Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002; 420:860–867
Hirsch HA, Iliopoulos D, Struhl K. Metformin inhibits the inflammatory response associated with cellular transformation and cancer stem cell growth. Proc Natl Acad Sci U S A. 2013; 110:972–977
Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB, Lipsky PE. Cyclooxygenase in biology and disease. FASEB J. 1998; 12:1063–1073
Greenhough A, Smartt HJ, Moore AE, Roberts HR, Williams AC, Paraskeva C, Kaidi A. The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcinogenesis. 2009; 30:377–386
Prima V, Kaliberova LN, Kaliberov S, Curiel DT, Kusmartsev S. COX2/mpges1/PGE2 pathway regulates PD-L1 expression in tumor-associated macrophages and myeloid-derived suppressor cells. Proc Natl Acad Sci U S A. 2017; 114:1117–1122
Botti G, Fratangelo F, Cerrone M, Liguori G, Cantile M, Anniciello AM, et al. COX-2 expression positively correlates with PD-L1 expression in human melanoma cells. J Transl Med. 2017; 15:46
Gallo C, Dallaglio K, Bassani B, Rossi T, Rossello A, Noonan DM, et al. Hop derived flavonoid xanthohumol inhibits endothelial cell functions via AMPK activation. Oncotarget. 2016; 7:59917–59931
Mussini C, Pinti M, Bugarini R, Borghi V, Nasi M, Nemes E, et al. Effect of treatment interruption monitored by CD4 cell count on mitochondrial DNA content in HIV-infected patients: a prospective study. AIDS. 2005; 19:1627–1633