Top

Breast Cancer Research and Treatment

Published in:

Open Access 01-07-2019 | Prostate Cancer | Preclinical study

A novel RNA aptamer identifies plasma membrane ATP synthase beta subunit as an early marker and therapeutic target in aggressive cancer

Authors: S. Speransky, P. Serafini, J. Caroli, S. Bicciato, M. E. Lippman, N. H. Bishopric

Published in: Breast Cancer Research and Treatment | Issue 2/2019

Abstract

Purpose

Primary breast and prostate cancers can be cured, but metastatic disease cannot. Identifying cell factors that predict metastatic potential could guide both prognosis and treatment.

Methods

We used Cell-SELEX to screen an RNA aptamer library for differential binding to prostate cancer cell lines with high vs. low metastatic potential. Mass spectroscopy, immunoblot, and immunohistochemistry were used to identify and validate aptamer targets. Aptamer properties were tested in vitro, in xenograft models, and in clinical biopsies. Gene expression datasets were queried for target associations in cancer.

Results

We identified a novel aptamer (Apt63) that binds to the beta subunit of F₁F_o ATP synthase (ATP5B), present on the plasma membrane of certain normal and cancer cells. Apt63 bound to plasma membranes of multiple aggressive breast and prostate cell lines, but not to normal breast and prostate epithelial cells, and weakly or not at all to non-metastasizing cancer cells; binding led to rapid cell death. A single intravenous injection of Apt63 induced rapid, tumor cell-selective binding and cytotoxicity in MDA-MB-231 xenograft tumors, associated with endonuclease G nuclear translocation and DNA fragmentation. Apt63 was not toxic to non-transformed epithelial cells in vitro or adjacent normal tissue in vivo. In breast cancer tissue arrays, plasma membrane staining with Apt63 correlated with tumor stage (p < 0.0001, n = 416) and was independent of other cancer markers. Across multiple datasets, ATP5B expression was significantly increased relative to normal tissue, and negatively correlated with metastasis-free (p = 0.0063, 0.00039, respectively) and overall (p = 0.050, 0.0198) survival.

Conclusion

Ecto-ATP5B binding by Apt63 may disrupt an essential survival mechanism in a subset of tumors with high metastatic potential, and defines a novel category of cancers with potential vulnerability to ATP5B-targeted therapy. Apt63 is a unique tool for elucidating the function of surface ATP synthase, and potentially for predicting and treating metastatic breast and prostate cancer.

Available only for authorised users

Ellis MJ, Perou CM (2013) The genomic landscape of breast cancer as a therapeutic roadmap. Cancer Discov 3:27–34. https://doi.org/10.1158/2159-8290.CD-12-0462 CrossRefPubMedPubMedCentral

Curtis C, Shah SP, Chin SF, Turashvili G, Rueda OM, Dunning MJ, Speed D, Lynch AG, Samarajiwa S, Yuan Y, Graf S, Ha G, Haffari G, Bashashati A, Russell R, McKinney S, Langerod A, Green A, Provenzano E, Wishart G, Pinder S, Watson P, Markowetz F, Murphy L, Ellis I, Purushotham A, Borresen-Dale AL, Brenton JD, Tavare S, Caldas C, Aparicio S (2012) The genomic and transcriptomic architecture of 2000 breast tumours reveals novel subgroups. Nature 486:346–352. https://doi.org/10.1038/nature10983 CrossRefPubMedPubMedCentral

Huang KL, Li S, Mertins P, Cao S, Gunawardena HP, Ruggles KV, Mani DR, Clauser KR, Tanioka M, Usary J, Kavuri SM, Xie L, Yoon C, Qiao JW, Wrobel J, Wyczalkowski MA, Erdmann-Gilmore P, Snider JE, Hoog J, Singh P, Niu B, Guo Z, Sun SQ, Sanati S, Kawaler E, Wang X, Scott A, Ye K, McLellan MD, Wendl MC, Malovannaya A, Held JM, Gillette MA, Fenyo D, Kinsinger CR, Mesri M, Rodriguez H, Davies SR, Perou CM, Ma C, Reid Townsend R, Chen X, Carr SA, Ellis MJ, Ding L (2017) Proteogenomic integration reveals therapeutic targets in breast cancer xenografts. Nat Commun 8:14864. https://doi.org/10.1038/ncomms14864 CrossRefPubMedPubMedCentral

Saunders EJ, Dadaev T, Leongamornlert DA, Al Olama AA, Benlloch S, Giles GG, Wiklund F, Gronberg H, Haiman CA, Schleutker J, Nordestgaard BG, Travis RC, Neal D, Pasayan N, Khaw KT, Stanford JL, Blot WJ, Thibodeau SN, Maier C, Kibel AS, Cybulski C, Cannon-Albright L, Brenner H, Park JY, Kaneva R, Batra J, Teixeira MR, Pandha H, Govindasami K, Muir K, Easton DF, Eeles RA, Kote-Jarai Z (2016) Gene and pathway level analyses of germline DNA-repair gene variants and prostate cancer susceptibility using the iCOGS-genotyping array. Br J Cancer 114:945–952. https://doi.org/10.1038/bjc.2016.50 CrossRefPubMedPubMedCentral

Markowitz SD, Nock NL, Schmit SL, Stadler ZK, Joseph V, Zhang L, Willis JE, Scacheri P, Veigl M, Adams MD, Raskin L, Sullivan JF, Stratton K, Shia J, Ellis N, Rennert HS, Manschreck C, Li L, Offit K, Elston RC, Rennert G, Gruber SB (2016) A germline variant on chromosome 4q31.1 associates with susceptibility to developing colon cancer metastasis. PLoS ONE 11:e0146435. https://doi.org/10.1371/journal.pone.0146435 CrossRefPubMedPubMedCentral

Haider MT, Taipaleenmaki H (2018) Targeting the metastatic bone microenvironment by microRNAs. Front Endocrinol 9:202. https://doi.org/10.3389/fendo.2018.00202 CrossRef

Chen W, Hoffmann AD, Liu H, Liu X (2018) Organotropism: new insights into molecular mechanisms of breast cancer metastasis. NPJ Precis Oncol 2:4. https://doi.org/10.1038/s41698-018-0047-0 CrossRefPubMedPubMedCentral

Wang YP, Lei QY (2018) Metabolic recoding of epigenetics in cancer. Cancer Commun (London England) 38:25. https://doi.org/10.1186/s40880-018-0302-3 CrossRef

Morita Y, Leslie M, Kameyama H, Volk DE, Tanaka T (2018) Aptamer therapeutics in cancer: current and future. Cancers (Basel) 10. https://doi.org/10.3390/cancers10030080

10.

Moser TL, Kenan DJ, Ashley TA, Roy JA, Goodman MD, Misra UK, Cheek DJ, Pizzo SV (2001) Endothelial cell surface F1-F0 ATP synthase is active in ATP synthesis and is inhibited by angiostatin. Proc Natl Acad Sci USA 98:6656–6661. https://doi.org/10.1073/pnas.131067798 CrossRefPubMedPubMedCentral

11.

Arakaki N, Nagao T, Niki R, Toyofuku A, Tanaka H, Kuramoto Y, Emoto Y, Shibata H, Magota K, Higuti T (2003) Possible role of cell surface H+ -ATP synthase in the extracellular ATP synthesis and proliferation of human umbilical vein endothelial cells. Mol Cancer Res 1:931–939PubMed

12.

Chi SL, Pizzo SV (2006) Cell surface F1Fo ATP synthase: a new paradigm? Ann Med 38:429–438. https://doi.org/10.1080/07853890600928698 CrossRefPubMed

13.

Mowery YM, Pizzo SV (2008) Targeting cell surface F1F0 ATP synthase in cancer therapy. Cancer Biol Ther 7:1836–1838CrossRefPubMed

14.

Wang WJ, Ma Z, Liu YW, He YQ, Wang YZ, Yang CX, Du Y, Zhou MQ, Gao F (2012) A monoclonal antibody (Mc178-Ab) targeted to the ecto-ATP synthase beta-subunit-induced cell apoptosis via a mechanism involving the MAPKase and Akt pathways. Clin Exp Med 12:3–12. https://doi.org/10.1007/s10238-011-0133-x CrossRefPubMed

15.

Chivasa S, Tome DF, Hamilton JM, Slabas AR (2011) Proteomic analysis of extracellular ATP-regulated proteins identifies ATP synthase beta-subunit as a novel plant cell death regulator. Mol Cell Proteom 10:M110.003905. https://doi.org/10.1074/mcp.M110.003905 CrossRef

16.

Villa-Pulgarin JA, Gajate C, Botet J, Jimenez A, Justies N, Varela MR, Cuesta-Marban A, Muller I, Modolell M, Revuelta JL, Mollinedo F (2017) Mitochondria and lipid raft-located FOF1-ATP synthase as major therapeutic targets in the antileishmanial and anticancer activities of ether lipid edelfosine. PLoS Negl Trop Dis 11:e0005805. https://doi.org/10.1371/journal.pntd.0005805 CrossRefPubMedPubMedCentral

17.

Lu ZJ, Song QF, Jiang SS, Song Q, Wang W, Zhang GH, Kan B, Chen LJ, Yang JL, Luo F, Qian ZY, Wei YQ, Gou LT (2009) Identification of ATP synthase beta subunit (ATPB) on the cell surface as a non-small cell lung cancer (NSCLC) associated antigen. BMC Cancer 9:16. https://doi.org/10.1186/1471-2407-9-16 CrossRefPubMedPubMedCentral

18.

Dowling P, Meleady P, Dowd A, Henry M, Glynn S, Clynes M (2007) Proteomic analysis of isolated membrane fractions from superinvasive cancer cells. Biochim Biophys Acta 1774:93–101. https://doi.org/10.1016/j.bbapap.2006.09.014 CrossRefPubMed

19.

Pettaway CA, Pathak S, Greene G, Ramirez E, Wilson MR, Killion JJ, Fidler IJ (1996) Selection of highly metastatic variants of different human prostatic carcinomas using orthotopic implantation in nude mice. Clin Cancer Res 2:1627–1636PubMed

20.

Drews-Elger K, Brinkman JA, Miller P, Shah SH, Harrell JC, da Silva TG, Ao Z, Schlater A, Azzam DJ, Diehl K, Thomas D, Slingerland JM, Perou CM, Lippman ME, El-Ashry D (2014) Primary breast tumor-derived cellular models: characterization of tumorigenic, metastatic, and cancer-associated fibroblasts in dissociated tumor (DT) cultures. Breast Cancer Res Treat. https://doi.org/10.1007/s10549-014-2887-9 CrossRefPubMed

21.

Young L, Sung J, Stacey G, Masters JR (2010) Detection of mycoplasma in cell cultures. Nat Protoc 5:929. https://doi.org/10.1038/nprot.2010.43 CrossRefPubMed

22.

Roth F, De La Fuente AC, Vella JL, Zoso A, Inverardi L, Serafini P (2012) Aptamer-mediated blockade of IL4Ralpha triggers apoptosis of MDSCs and limits tumor progression. Cancer Res 72:1373–1383. https://doi.org/10.1158/0008-5472.CAN-11-2772 CrossRefPubMed

23.

Hoinka J, Zotenka E, Friedman A, Sauna ZE, Przytycka TM (2012) Identification of sequence-structure RNA binding motifs for SELEX-derived aptamers. Bioinformatics 28(12):i215–i223. https://doi.org/10.1093/bioinformatics/bts210 doiCrossRefPubMedPubMedCentral

24.

Iorns E, Drews-Elger K, Ward TM, Dean S, Clarke J, Berry D, El Ashry D, Lippman M (2012) A new mouse model for the study of human breast cancer metastasis. PLoS One 7:e47995. https://doi.org/10.1371/journal.pone.0047995 CrossRefPubMedPubMedCentral

25.

Abeshouse A, Ahn J, Akbani R, Ally A, Amin S, Andry CD, Annala M, Aprikian A, Armenia J, Arora A, Auman JT (2015) The molecular taxonomy of primary prostate cancer. Cell 163:1011–1025. https://doi.org/10.1016/j.cell.2015.10.025 CrossRef

26.

Penney KL, Sinnott JA, Tyekucheva S, Gerke T, Shui IM, Kraft P, Sesso HD, Freedman ML, Loda M, Mucci LA, Stampfer MJ (2015) Association of prostate cancer risk variants with gene expression in normal and tumor tissue. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research. Am Soc Prev Oncol 24:255–260. https://doi.org/10.1158/1055-9965.Epi-14-0694-t CrossRef

27.

Erho N, Crisan A, Vergara IA, Mitra AP, Ghadessi M, Buerki C, Bergstralh EJ, Kollmeyer T, Fink S, Haddad Z, Zimmermann B, Sierocinski T, Ballman KV, Triche TJ, Black PC, Karnes RJ, Klee G, Davicioni E, Jenkins RB (2013) Discovery and validation of a prostate cancer genomic classifier that predicts early metastasis following radical prostatectomy. PLoS One 8:e66855. https://doi.org/10.1371/journal.pone.0066855 CrossRefPubMedPubMedCentral

28.

Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, Speed TP (2003) Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics (Oxford England) 4:249–264. https://doi.org/10.1093/biostatistics/4.2.249 CrossRef

29.

Chang JW, Kuo WH, Lin CM, Chen WL, Chan SH, Chiu MF, Chang IS, Jiang SS, Tsai FY, Chen CH, Huang PH, Chang KJ, Lin KT, Lin SC, Wang MY, Uen YH, Tu CW, Hou MF, Tsai SF, Shen CY, Tung SL, Wang LH (2018) Wild-type p53 upregulates an early onset breast cancer-associated gene GAS7 to suppress metastasis via GAS7-CYFIP1-mediated signaling pathway. Oncogene 37:4137–4150. https://doi.org/10.1038/s41388-018-0253-9 CrossRefPubMedPubMedCentral

30.

(2012) Comprehensive molecular portraits of human breast tumours. Nature 490:61–70. https://doi.org/10.1038/nature11412

31.

Cordenonsi M, Zanconato F, Azzolin L, Forcato M, Rosato A, Frasson C, Inui M, Montagner M, Parenti AR, Poletti A, Daidone MG, Dupont S, Basso G, Bicciato S, Piccolo S (2011) The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. Cell 147:759–772. https://doi.org/10.1016/j.cell.2011.09.048 CrossRefPubMed

32.

Enzo E, Santinon G, Pocaterra A, Aragona M, Bresolin S, Forcato M, Grifoni D, Pession A, Zanconato F, Guzzo G, Bicciato S, Dupont S (2015) Aerobic glycolysis tunes YAP/TAZ transcriptional activity. Embo J 34:1349–1370. https://doi.org/10.15252/embj.201490379 CrossRefPubMedPubMedCentral

33.

Adorno M, Cordenonsi M, Montagner M, Dupont S, Wong C, Hann B, Solari A, Bobisse S, Rondina MB, Guzzardo V, Parenti AR, Rosato A, Bicciato S, Balmain A, Piccolo S (2009) A Mutant-p53/Smad complex opposes p63 to empower TGFbeta-induced metastasis. Cell 137:87–98. https://doi.org/10.1016/j.cell.2009.01.039 CrossRefPubMed

34.

Sievers F, Wilm A, Dineen D, Gibson TJ, Karplus K, Li W, Lopez R, McWilliam H, Remmert M, Soding J, Thompson JD, Higgins DG (2011) Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol 7:539. https://doi.org/10.1038/msb.2011.75 CrossRefPubMedPubMedCentral

35.

Ahmad Z, Laughlin TF (2010) Medicinal chemistry of ATP synthase: a potential drug target of dietary polyphenols and amphibian antimicrobial peptides. Curr Med Chem 17:2822–2836CrossRefPubMedPubMedCentral

36.

Widlak P, Li LY, Wang X, Garrard WT (2001) Action of recombinant human apoptotic endonuclease G on naked DNA and chromatin substrates: cooperation with exonuclease and DNase I. J Biol Chem 276:48404–48409. https://doi.org/10.1074/jbc.M108461200 CrossRefPubMed

37.

Li LY, Luo X, Wang X (2001) Endonuclease G is an apoptotic DNase when released from mitochondria. Nature 412:95–99. https://doi.org/10.1038/35083620 CrossRefPubMed

38.

Willers IM, Martinez-Reyes I, Martinez-Diez M, Cuezva JM (2012) miR-127-5p targets the 3′UTR of human beta-F1-ATPase mRNA and inhibits its translation. Biochim Biophys Acta 1817:838–848. https://doi.org/10.1016/j.bbabio.2012.03.005 CrossRefPubMed

39.

Delic V, Brownlow M, Joly-Amado A, Zivkovic S, Noble K, Phan TA, Ta Y, Zhang Y, Bell SD, Kurien C, Reynes C, Morgan D, Bradshaw PC (2015) Calorie restriction does not restore brain mitochondrial function in P301L tau mice, but it does decrease mitochondrial F0F1-ATPase activity. Mol Cell Neurosci 67:46–54. https://doi.org/10.1016/j.mcn.2015.06.001 CrossRefPubMed

40.

Tanton H, Voronina S, Evans A, Armstrong J, Sutton R, Criddle DN, Haynes L, Schmid MC, Campbell F, Costello E, Tepikin AV (2018) F1F0-ATP synthase inhibitory factor 1 in the normal pancreas and in pancreatic ductal adenocarcinoma: effects on bioenergetics, invasion and proliferation. Front Physiol 9:833. https://doi.org/10.3389/fphys.2018.00833 CrossRefPubMedPubMedCentral

41.

Williams EG, Wu Y, Wolski W, Kim JY, Lan J, Hasan M, Halter C, Jha P, Ryu D, Auwerx J, Aebersold R (2018) Quantifying and localizing the mitochondrial proteome across five tissues in a mouse population. Mol Cell Proteom 17:1766–1777. https://doi.org/10.1074/mcp.RA118.000554 CrossRef

42.

Pan J, Sun LC, Tao YF, Zhou Z, Du XL, Peng L, Feng X, Wang J, Li YP, Liu L, Wu SY, Zhang YL, Hu SY, Zhao WL, Zhu XM, Lou GL, Ni J (2011) ATP synthase ecto-alpha-subunit: a novel therapeutic target for breast cancer. J Transl Med 9:211. https://doi.org/10.1186/1479-5876-9-211 CrossRefPubMedPubMedCentral

43.

Xiaoyun X, Chaofei H, Weiqi Z, Chen C, Lixia L, Queping L, Cong P, Shuang Z, Juan S, Xiang C (2017) Possible involvement of F1F0-ATP synthase and intracellular ATP in keratinocyte differentiation in normal skin and skin lesions. Sci Rep 7:42672. https://doi.org/10.1038/srep42672 CrossRefPubMedPubMedCentral

44.

Pedersen PL, Amzel LM (1993) ATP synthases. Structure, reaction center, mechanism, and regulation of one of nature’s most unique machines. J Biol Chem 268:9937–9940PubMed

45.

Pedersen PL, Ko YH, Hong S (2000) ATP synthases in the year 2000: defining the different levels of mechanism and getting a grip on each. J Bioenerg Biomembr 32:423–432CrossRefPubMed

46.

Hong S, Pedersen PL (2008) ATP synthase and the actions of inhibitors utilized to study its roles in human health, disease, and other scientific areas. Microbiol Mol Biol Rev 72:590–641. https://doi.org/10.1128/MMBR.00016-08 CrossRefPubMedPubMedCentral

47.

Gledhill JR, Montgomery MG, Leslie AG, Walker JE (2007) Mechanism of inhibition of bovine F1-ATPase by resveratrol and related polyphenols. Proc Natl Acad Sci USA 104:13632–13637. https://doi.org/10.1073/pnas.0706290104 CrossRefPubMedPubMedCentral

48.

Das B, Mondragon MO, Sadeghian M, Hatcher VB, Norin AJ (1994) A novel ligand in lymphocyte-mediated cytotoxicity: expression of the beta subunit of H + transporting ATP synthase on the surface of tumor cell lines. J Exp Med 180:273–281CrossRefPubMed

49.

Cavelier C, Ohnsorg PM, Rohrer L, von Eckardstein A (2012) The beta-chain of cell surface F(0)F(1) ATPase modulates apoA-I and HDL transcytosis through aortic endothelial cells. Arterioscler Thromb Vasc Biol 32:131–139. https://doi.org/10.1161/ATVBAHA.111.238063 CrossRefPubMed

50.

Martinez LO, Jacquet S, Esteve JP, Rolland C, Cabezon E, Champagne E, Pineau T, Georgeaud V, Walker JE, Terce F, Collet X, Perret B, Barbaras R (2003) Ectopic beta-chain of ATP synthase is an apolipoprotein A-I receptor in hepatic HDL endocytosis. Nature 421:75–79. https://doi.org/10.1038/nature01250 CrossRefPubMed

51.

Gonzalez-Pecchi V, Valdes S, Pons V, Honorato P, Martinez LO, Lamperti L, Aguayo C, Radojkovic C (2015) Apolipoprotein A-I enhances proliferation of human endothelial progenitor cells and promotes angiogenesis through the cell surface ATP synthase. Microvasc Res 98:9–15. https://doi.org/10.1016/j.mvr.2014.11.003 CrossRefPubMed

52.

Veitonmaki N, Cao R, Wu LH, Moser TL, Li B, Pizzo SV, Zhivotovsky B, Cao Y (2004) Endothelial cell surface ATP synthase-triggered caspase-apoptotic pathway is essential for k1-5-induced antiangiogenesis. Cancer Res 64:3679–3686. https://doi.org/10.1158/0008-5472.CAN-03-1754 CrossRefPubMed

53.

Wajih N, Sane DC (2003) Angiostatin selectively inhibits signaling by hepatocyte growth factor in endothelial and smooth muscle cells. Blood 101:1857–1863. https://doi.org/10.1182/blood-2002-02-0582 CrossRefPubMed

54.

Goretzki L, Lombardo CR, Stallcup WB (2000) Binding of the NG2 proteoglycan to kringle domains modulates the functional properties of angiostatin and plasmin(ogen). J Biol Chem 275:28625–28633. https://doi.org/10.1074/jbc.M002290200 CrossRefPubMed

55.

Tuszynski GP, Sharma MR, Rothman VL, Sharma MC (2002) Angiostatin binds to tyrosine kinase substrate annexin II through the lysine-binding domain in endothelial cells. Microvasc Res 64:448–462CrossRefPubMed

56.

Muller WEG, Ackermann M, Tolba E, Neufurth M, Ivetac I, Kokkinopoulou M, Schroder HC, Wang X (2018) Role of ATP during the initiation of microvascularization: acceleration of an autocrine sensing mechanism facilitating chemotaxis by inorganic polyphosphate. Biochem J 475:3255–3273. https://doi.org/10.1042/bcj20180535 CrossRefPubMed

57.

Song R, Harris LD, Pettaway CA (2010) Downmodulation of Bcl-2 sensitizes metastatic LNCaP-LN3 cells to undergo apoptosis via the intrinsic pathway. Prostate 70:571–583. https://doi.org/10.1002/pros.21091 CrossRefPubMed

58.

Karan D, Chen SJ, Johansson SL, Singh AP, Paralkar VM, Lin MF, Batra SK (2003) Dysregulated expression of MIC-1/PDF in human prostate tumor cells. Biochem Biophys Res Commun 305:598–604CrossRefPubMed

59.

Glen A, Gan CS, Hamdy FC, Eaton CL, Cross SS, Catto JW, Wright PC, Rehman I (2008) iTRAQ-facilitated proteomic analysis of human prostate cancer cells identifies proteins associated with progression. J Proteome Res 7:897–907. https://doi.org/10.1021/pr070378x CrossRefPubMed

60.

Balbay MD, Pettaway CA, Kuniyasu H, Inoue K, Ramirez E, Li E, Fidler IJ, Dinney CP (1999) Highly metastatic human prostate cancer growing within the prostate of athymic mice overexpresses vascular endothelial growth factor. Clin Cancer Res 5:783–789PubMed

61.

Chu LW, Pettaway CA, Liang JC (2001) Genetic abnormalities specifically associated with varying metastatic potential of prostate cancer cell lines as detected by comparative genomic hybridization. Cancer Genet Cytogenet 127:161–167CrossRefPubMed

62.

Damola A, Legendre A, Ball S, Masters JR, Williamson M (2013) Function of mutant and wild-type plexinb1 in prostate cancer cells. Prostate 73:1326–1335. https://doi.org/10.1002/pros.22678 CrossRefPubMedPubMedCentral

63.

Glen A, Evans CA, Gan CS, Cross SS, Hamdy FC, Gibbins J, Lippitt J, Eaton CL, Noirel J, Wright PC, Rehman I (2010) Eight-plex iTRAQ analysis of variant metastatic human prostate cancer cells identifies candidate biomarkers of progression: An exploratory study. Prostate 70:1313–1332. https://doi.org/10.1002/pros.21167 CrossRefPubMed

64.

Li W, Li Y, Li G, Zhou Z, Chang X, Xia Y, Dong X, Liu Z, Ren B, Liu W, Li Y (2017) Ectopic expression of the ATP synthase beta subunit on the membrane of PC-3M cells supports its potential role in prostate cancer metastasis. Int J Oncol 50:1312–1320. https://doi.org/10.3892/ijo.2017.3878 CrossRefPubMed

65.

Wang J, Han Y, Liang J, Cheng X, Yan L, Wang Y, Liu J, Luo G, Cheng X, Zhao L, Zhou X, Wu K, Fan D (2008) Effect of a novel inhibitory mAb antibody against β-subunit of F1F0 ATPase on HCC. Cancer Biol Ther 7:1829–1835. https://doi.org/10.4161/cbt.7.11.6861 CrossRefPubMed

66.

Chang HY, Huang HC, Huang TC, Yang PC, Wang YC, Juan HF (2012) Ectopic ATP synthase blockade suppresses lung adenocarcinoma growth by activating the unfolded protein response. Cancer Res 72:4696–4706. https://doi.org/10.1158/0008-5472.CAN-12-0567 CrossRefPubMed

67.

Hu CW, Hsu CL, Wang YC, Ishihama Y, Ku WC, Huang HC, Juan HF (2015) Temporal phosphoproteome dynamics induced by an ATP synthase inhibitor citreoviridin. Mol Cell Proteom 14:3284–3298. https://doi.org/10.1074/mcp.M115.051383 CrossRef

68.

Chi SL, Pizzo SV (2006) Angiostatin is directly cytotoxic to tumor cells at low extracellular pH: a mechanism dependent on cell surface-associated ATP synthase. Cancer Res 66(2):875–882. https://doi.org/10.1158/0008-5472.CAN-05-2806 CrossRefPubMed

69.

Zhang X, Gao F, Yu LL, Peng Y, Liu HH, Liu JY, Yin M, Ni J (2008) Dual functions of a monoclonal antibody against cell surface F1F0 ATP synthase on both HUVEC and tumor cells. Acta Pharmacol Sin 29:942–950. https://doi.org/10.1111/j.1745-7254.2008.00830.x CrossRefPubMed

70.

Kagawa Y, Ohta S (1990) Regulation of mitochondrial ATP synthesis in mammalian cells by transcriptional control. Int J Biochem 22:219–229CrossRefPubMed

71.

Singh S, Khar A (2005) Differential gene expression during apoptosis induced by a serum factor: role of mitochondrial F0-F1 ATP synthase complex. Apoptosis 10:1469–1482. https://doi.org/10.1007/s10495-005-1394-1 CrossRefPubMed

72.

Campanella M, Casswell E, Chong S, Farah Z, Wieckowski MR, Abramov AY, Tinker A, Duchen MR (2008) Regulation of mitochondrial structure and function by the F1Fo-ATPase inhibitor protein, IF1. Cell Metab 8:13–25. https://doi.org/10.1016/j.cmet.2008.06.001 CrossRefPubMed

73.

Yamamoto K, Shimizu N, Obi S, Kumagaya S, Taketani Y, Kamiya A, Ando J (2007) Involvement of cell surface ATP synthase in flow-induced ATP release by vascular endothelial cells. Am J Physiol Heart Circ Physiol 293:H1646–H1653. https://doi.org/10.1152/ajpheart.01385.2006 CrossRefPubMed

74.

Vanaja DK, Cheville JC, Iturria SJ, Young CY (2003) Transcriptional silencing of zinc finger protein 185 identified by expression profiling is associated with prostate cancer progression. Cancer Res 63:3877–3882PubMed

Title: A novel RNA aptamer identifies plasma membrane ATP synthase beta subunit as an early marker and therapeutic target in aggressive cancer
Authors: S. Speransky
P. Serafini
J. Caroli
S. Bicciato
M. E. Lippman
N. H. Bishopric
Publication date: 01-07-2019
Publisher: Springer US
Keywords: Prostate Cancer
Metastasis
Breast Cancer
Prostate Cancer
Breast Cancer
Published in: Breast Cancer Research and Treatment / Issue 2/2019
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-019-05174-3

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 2/2019

Post-mastectomy immediate breast reconstruction is oncologically safe in well-selected T4 locally advanced breast cancer: a large population-based study and matched case–control analysis

Examining the cost-effectiveness of baseline left ventricular function assessment among breast cancer patients undergoing anthracycline-based therapy

Childbirth in young Korean women with previously treated breast cancer: The SMARTSHIP study

Comparing long-term local recurrence rates of surgical and non-surgical management of close anterior margins in breast conserving surgery

Examination and prognostic implications of the unique microenvironment of breast cancer brain metastases

Vinorelbine plus Capecitabine (Vinocap): a retrospective analysis in heavily pretreated HER2 negative metastatic breast cancer patients

Keynote webinar | Spotlight on antibody–drug conjugates in cancer