Autophagy regulation and its dual role in blood cancers: A novel target for therapeutic development (Review)
- Authors:
- Shenhe Jin
- Juying Wei
- Liangshun You
- Hui Liu
- Wenbin Qian
-
Affiliations: Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China, Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China - Published online on: April 13, 2018 https://doi.org/10.3892/or.2018.6370
- Pages: 2473-2481
This article is mentioned in:
Abstract
Dong Z, Liang S, Hu J, Jin W, Zhan Q and Zhao K: Autophagy as a target for hematological malignancy therapy. Blood Rev. 30:369–380. 2016. View Article : Google Scholar | |
Helgason GV, Holyoake TL and Ryan KM: Role of autophagy in cancer prevention, development and therapy. Essays Biochem. 55:133–151. 2013. View Article : Google Scholar | |
Duffy A, Le J, Sausville E and Emadi A: Autophagy modulation: A target for cancer treatment development. Cancer Chemother Pharmacol. 75:439–447. 2015. View Article : Google Scholar | |
Klionsky DJ: The molecular machinery of autophagy: Unanswered questions. J Cell Sci. 118:7–18. 2005. View Article : Google Scholar | |
Hosokawa N, Hara T, Kaizuka T, Kishi C, Takamura A, Miura Y, Iemura S, Natsume T, Takehana K, Yamada N, et al: Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol Biol Cell. 20:1981–1991. 2009. View Article : Google Scholar | |
Jung CH, Jun CB, Ro SH, Kim YM, Otto NM, Cao J, Kundu M and Kim DH: ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell. 20:1992–2003. 2009. View Article : Google Scholar | |
Devereaux K, Dall'Armi C, Alcazar-Roman A, Ogasawara Y, Zhou X, Wang F, Yamamoto A, De Camilli P and Di Paolo G: Regulation of mammalian autophagy by class II and III PI 3-kinases through PI3P synthesis. PLoS One. 8:e764052013. View Article : Google Scholar | |
Petibone DM, Majeed W and Casciano DA: Autophagy function and its relationship to pathology, clinical applications, drug metabolism and toxicity. J Appl Toxicol. 37:23–37. 2017. View Article : Google Scholar | |
Hamasaki M, Shibutani ST and Yoshimori T: Up-to-date membrane biogenesis in the autophagosome formation. Curr Opin Cell Biol. 25:455–460. 2013. View Article : Google Scholar | |
Fujita N, Itoh T, Omori H, Fukuda M, Noda T and Yoshimori T: The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy. Mol Biol Cell. 19:2092–2100. 2008. View Article : Google Scholar | |
Hanada T, Noda NN, Satomi Y, Ichimura Y, Fujioka Y, Takao T, Inagaki F and Ohsumi Y: The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy. J Biol Chem. 282:37298–37302. 2007. View Article : Google Scholar | |
Geng J and Klionsky DJ: The Atg8 and Atg12 ubiquitin-like conjugation systems in macroautophagy. ‘Protein modifications: Beyond the usual suspects’ review series. EMBO Rep. 9:859–864. 2008. View Article : Google Scholar | |
Weidberg H, Shvets E, Shpilka T, Shimron F, Shinder V and Elazar Z: LC3 and GATE-16/GABARAP subfamilies are both essential yet act differently in autophagosome biogenesis. EMBO J. 29:1792–1802. 2010. View Article : Google Scholar | |
Chua CE, Gan BQ and Tang BL: Involvement of members of the Rab family and related small GTPases in autophagosome formation and maturation. Cell Mol Life Sci. 68:3349–3358. 2011. View Article : Google Scholar | |
Liang C, Lee JS, Inn KS, Gack MU, Li Q, Roberts EA, Vergne I, Deretic V, Feng P, Akazawa C, et al: Beclin1-binding UVRAG targets the class C Vps complex to coordinate autophagosome maturation and endocytic trafficking. Nat Cell Biol. 10:776–787. 2008. View Article : Google Scholar | |
Pan H, Chen L, Xu Y, Han W, Lou F, Fei W, Liu S, Jing Z and Sui X: Autophagy-associated immune responses and cancer immunotherapy. Oncotarget. 7:21235–21246. 2016. | |
Stellrecht CM, Vangapandu HV, Le XF, Mao W and Shentu S: ATP directed agent, 8-chloro-adenosine, induces AMP activated protein kinase activity, leading to autophagic cell death in breast cancer cells. J Hematol Oncol. 7:232014. View Article : Google Scholar | |
Baehrecke EH: Autophagy: Dual roles in life and death? Nat Rev Mol Cell Biol. 6:505–510. 2005. View Article : Google Scholar | |
Gozuacik D and Kimchi A: Autophagy as a cell death and tumor suppressor mechanism. Oncogene. 23:2891–2906. 2004. View Article : Google Scholar | |
Bursch W: The autophagosomal-lysosomal compartment in programmed cell death. Cell Death Differ. 8:569–581. 2001. View Article : Google Scholar | |
Lin L and Baehrecke EH: Autophagy, cell death, and cancer. Mol Cell Oncol. 2:e9859132015. View Article : Google Scholar | |
Scott RC, Juhász G and Neufeld TP: Direct induction of autophagy by Atg1 inhibits cell growth and induces apoptotic cell death. Curr Biol. 17:1–11. 2007. View Article : Google Scholar | |
Yu L, Wan F, Dutta S, Welsh S, Liu Z, Freundt E, Baehrecke EH and Lenardo M: Autophagic programmed cell death by selective catalase degradation. Proc Natl Acad Sci USA. 103:4952–4957. 2006. View Article : Google Scholar | |
Nezis IP, Shravage BV, Sagona AP, Lamark T, Bjørkøy G, Johansen T, Rusten TE, Brech A, Baehrecke EH and Stenmark H: Autophagic degradation of dBruce controls DNA fragmentation in nurse cells during late Drosophila melanogaster oogenesis. J Cell Biol. 190:523–531. 2010. View Article : Google Scholar | |
Petiot A, Ogier-Denis E, Blommaart EF, Meijer AJ and Codogno P: Distinct classes of phosphatidylinositol 3-kinases are involved in signaling pathways that control macroautophagy in HT-29 cells. J Biol Chem. 275:992–998. 2000. View Article : Google Scholar | |
Hanada M, Feng J and Hemmings BA: Structure, regulation and function of PKB/AKT - a major therapeutic target. Biochim Biophys Acta. 1697:3–16. 2004. View Article : Google Scholar | |
Yu X, Long YC and Shen HM: Differential regulatory functions of three classes of phosphatidylinositol and phosphoinositide 3-kinases in autophagy. Autophagy. 11:1711–1728. 2015. View Article : Google Scholar | |
McKnight NC and Zhenyu Y: Beclin 1, an essential component and master regulator of PI3K-III in health and disease. Curr Pathobiol Rep. 1:231–238. 2013. View Article : Google Scholar | |
Boya P, González-Polo RA, Casares N, Perfettini JL, Dessen P, Larochette N, Métivier D, Meley D, Souquere S, Yoshimori T, et al: Inhibition of macroautophagy triggers apoptosis. Mol Cell Biol. 25:1025–1040. 2005. View Article : Google Scholar | |
Ogata M, Hino S, Saito A, Morikawa K, Kondo S, Kanemoto S, Murakami T, Taniguchi M, Tanii I, Yoshinaga K, et al: Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol. 26:9220–9231. 2006. View Article : Google Scholar | |
Moretti L, Yang ES, Kim KW and Lu B: Autophagy signaling in cancer and its potential as novel target to improve anticancer therapy. Drug Resist Updat. 10:135–143. 2007. View Article : Google Scholar | |
Ron D: Translational control in the endoplasmic reticulum stress response. J Clin Invest. 110:1383–1388. 2002. View Article : Google Scholar | |
Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A, Vasquez DS, Turk BE and Shaw RJ: AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell. 30:214–226. 2008. View Article : Google Scholar | |
Schmukler E, Kloog Y and Pinkas-Kramarski R: Ras and autophagy in cancer development and therapy. Oncotarget. 5:577–586. 2014. View Article : Google Scholar | |
Downward J: Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer. 3:11–22. 2003. View Article : Google Scholar | |
Byun JY, Yoon CH, An S, Park IC, Kang CM, Kim MJ and Lee SJ: The Rac1/MKK7/JNK pathway signals upregulation of Atg5 and subsequent autophagic cell death in response to oncogenic Ras. Carcinogenesis. 30:1880–1888. 2009. View Article : Google Scholar | |
Pattingre S, Tassa A, Qu X, Garuti R, Liang XH, Mizushima N, Packer M, Schneider MD and Levine B: Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell. 122:927–939. 2005. View Article : Google Scholar | |
Levine B, Sinha SC and Kroemer G: Bcl-2 family members: Dual regulators of apoptosis and autophagy. Autophagy. 4:600–606. 2008. View Article : Google Scholar | |
Inbal B, Bialik S, Sabanay I, Shani G and Kimchi A: DAP kinase and DRP-1 mediate membrane blebbing and the formation of autophagic vesicles during programmed cell death. J Cell Biol. 157:455–468. 2002. View Article : Google Scholar | |
Zeng X, Yan T, Schupp JE, Seo Y and Kinsella TJ: DNA mismatch repair initiates 6-thioguanine-induced autophagy through p53 activation in human tumor cells. Clin Cancer Res. 13:1315–1321. 2007. View Article : Google Scholar | |
Auberger P and Puissant A: Autophagy, a key mechanism of oncogenesis and resistance in leukemia. Blood. 129:547–552. 2017. View Article : Google Scholar | |
Liu T, Zhang Z, Yu C, Zeng C, Xu X, Wu G, Huang Z and Li W: Tetrandrine antagonizes acute megakaryoblastic leukemia growth by forcing autophagy-mediated differentiation. Br J Pharmacol. 174:4308–4328. 2017. View Article : Google Scholar | |
Schläfli AM, Isakson P, Garattini E, Simonsen A and Tschan MP: The autophagy scaffold protein ALFY is critical for the granulocytic differentiation of AML cells. Sci Rep. 7:129802017. View Article : Google Scholar | |
Pierdominici M, Barbati C, Vomero M, Locatelli SL, Carlo-Stella C, Ortona E and Malorni W: Autophagy as a pathogenic mechanism and drug target in lymphoproliferative disorders. FASEB J. 28:524–535. 2014. View Article : Google Scholar | |
Zhang H, Pang Y, Ma C, Li J, Wang H and Shao Z: ClC5 decreases the sensitivity of multiple myeloma cells to bortezomib via promoting pro-survival autophagy. Oncol Res. Sep 11–2017.(Epub ahead of print). doi: 10.3727/096504017X15049221237147. View Article : Google Scholar | |
Yun Z, Zhichao J, Hao Y, Ou J, Ran Y, Wen D and Qun S: Targeting autophagy in multiple myeloma. Leuk Res. 59:97–104. 2017. View Article : Google Scholar | |
Mahoney E, Lucas DM, Gupta SV, Wagner AJ, Herman SE, Smith LL, Yeh YY, Andritsos L, Jones JA, Flynn JM, et al: ER stress and autophagy: New discoveries in the mechanism of action and drug resistance of the cyclin-dependent kinase inhibitor flavopiridol. Blood. 120:1262–1273. 2012. View Article : Google Scholar | |
Sharma A, Singh K, Mazumder S, Hill BT, Kalaycio M and Almasan A: BECN1 and BIM interactions with MCL-1 determine fludarabine resistance in leukemic B cells. Cell Death Dis. 4:e6282013. View Article : Google Scholar | |
Zakikhani M, Dowling RJ, Sonenberg N and Pollak MN: The effects of adiponectin and metformin on prostate and colon neoplasia involve activation of AMP-activated protein kinase. Cancer Prev Res. 1:369–375. 2008. View Article : Google Scholar | |
Wang LW, Li ZS, Zou DW, Jin ZD, Gao J and Xu GM: Metformin induces apoptosis of pancreatic cancer cells. World J Gastroenterol. 14:7192–7198. 2008. View Article : Google Scholar | |
Wang F, Liu Z, Zeng J, Zhu H, Li J, Cheng X, Jiang T, Zhang L, Zhang C, Chen T, et al: Metformin synergistically sensitizes FLT3-ITD-positive acute myeloid leukemia to sorafenib by promoting mTOR-mediated apoptosis and autophagy. Leuk Res. 39:1421–1427. 2015. View Article : Google Scholar | |
Shi WY, Xiao D, Wang L, Dong LH, Yan ZX, Shen ZX, Chen SJ, Chen Y and Zhao WL: Therapeutic metformin/AMPK activation blocked lymphoma cell growth via inhibition of mTOR pathway and induction of autophagy. Cell Death Dis. 3:e2752012. View Article : Google Scholar | |
Xia D, Zhang YT, Xu GP, Yan WW, Pan XR and Tong JH: Sertraline exerts its antitumor functions through both apoptosis and autophagy pathways in acute myeloid leukemia cells. Leuk Lymphoma. 58:1–10. 2017. View Article : Google Scholar | |
Trocoli A, Mathieu J, Priault M, Reiffers J, Souquère S, Pierron G, Besançon F and Djavaheri-Mergny M: ATRA-induced upregulation of Beclin 1 prolongs the life span of differentiated acute promyelocytic leukemia cells. Autophagy. 7:1108–1114. 2011. View Article : Google Scholar | |
Nishioka C, Ikezoe T, Yang J, Gery S, Koeffler HP and Yokoyama A: Inhibition of mammalian target of rapamycin signaling potentiates the effects of all-trans retinoic acid to induce growth arrest and differentiation of human acute myelogenous leukemia cells. Int J Cancer. 125:1710–1720. 2009. View Article : Google Scholar | |
Isakson P, Bjørås M, Bøe SO and Simonsen A: Autophagy contributes to therapy-induced degradation of the PML/RARA oncoprotein. Blood. 116:2324–2331. 2010. View Article : Google Scholar | |
Eriksen AB, Torgersen ML, Holm KL, Abrahamsen G, Spurkland A, Moskaug JØ, Simonsen A and Blomhoff HK: Retinoic acid-induced IgG production in TLR-activated human primary B cells involves ULK1-mediated autophagy. Autophagy. 11:460–471. 2015. View Article : Google Scholar | |
Qian W, Liu J, Jin J, Ni W and Xu W: Arsenic trioxide induces not only apoptosis but also autophagic cell death in leukemia cell lines via up-regulation of Beclin-1. Leuk Res. 31:329–339. 2007. View Article : Google Scholar | |
Goussetis DJ, Altman JK, Glaser H, McNeer JL, Tallman MS and Platanias LC: Autophagy is a critical mechanism for the induction of the antileukemic effects of arsenic trioxide. J Biol Chem. 285:29989–29997. 2010. View Article : Google Scholar | |
Ristic B, Bosnjak M, Arsikin K, Mircic A, Suzin-Zivkovic V, Bogdanovic A, Perovic V, Martinovic T, Kravic-Stevovic T, Bumbasirevic V, et al: Idarubicin induces mTOR-dependent cytotoxic autophagy in leukemic cells. Exp Cell Res. 326:90–102. 2014. View Article : Google Scholar | |
Grandér D, Kharaziha P, Laane E, Pokrovskaja K and Panaretakis T: Autophagy as the main means of cytotoxicity by glucocorticoids in hematological malignancies. Autophagy. 5:1198–1200. 2009. View Article : Google Scholar | |
Laane E, Tamm KP, Buentke E, Ito K, Kharaziha P, Oscarsson J, Corcoran M, Björklund AC, Hultenby K, Lundin J, et al: Cell death induced by dexamethasone in lymphoid leukemia is mediated through initiation of autophagy. Cell Death Differ. 16:1018–1029. 2009. View Article : Google Scholar | |
Granato M, Chiozzi B, Filardi MR, Lotti LV, Di Renzo L, Faggioni A and Cirone M: Tyrosine kinase inhibitor tyrphostin AG490 triggers both apoptosis and autophagy by reducing HSF1 and Mcl-1 in PEL cells. Cancer Lett. 366:191–197. 2015. View Article : Google Scholar | |
Germain M, Nguyen AP, Le Grand JN, Arbour N, Vanderluit JL, Park DS, Opferman JT and Slack RS: MCL-1 is a stress sensor that regulates autophagy in a developmentally regulated manner. EMBO J. 30:395–407. 2011. View Article : Google Scholar | |
Granato M, Lacconi V, Peddis M, Lotti LV, Di Renzo L, Gonnella R, Santarelli R, Trivedi P, Frati L, D'Orazi G, et al: HSP70 inhibition by 2-phenylethynesulfonamide induces lysosomal cathepsin D release and immunogenic cell death in primary effusion lymphoma. Cell Death Dis. 4:e7302013. View Article : Google Scholar | |
Crowley LC, Elzinga BM, O'Sullivan GC and McKenna SL: Autophagy induction by Bcr-Abl-expressing cells facilitates their recovery from a targeted or nontargeted treatment. Am J Hematol. 86:38–47. 2011. View Article : Google Scholar | |
Rothe K, Lin H, Lin KB, Leung A, Wang HM, Malekesmaeili M, Brinkman RR, Forrest DL, Gorski SM and Jiang X: The core autophagy protein ATG4B is a potential biomarker and therapeutic target in CML stem/progenitor cells. Blood. 123:3622–3634. 2014. View Article : Google Scholar | |
Mancini M, Leo E, Campi V, Castagnetti F, Zazzeroni L, Gugliotta G, Santucci MA and Martinelli G: A calpain-cleaved fragment of β-catenin promotes BCRABL1+ cell survival evoked by autophagy induction in response to imatinib. Cell Signal. 26:1690–1697. 2014. View Article : Google Scholar | |
Sheng Z, Ma L, Sun JE, Zhu LJ and Green MR: BCR-ABL suppresses autophagy through ATF5-mediated regulation of mTOR transcription. Blood. 118:2840–2848. 2011. View Article : Google Scholar | |
Xin P, Li C, Zheng Y, Peng Q, Xiao H, Huang Y and Zhu X: Efficacy of the dual PI3K and mTOR inhibitor NVP-BEZ235 in combination with imatinib mesylate against chronic myelogenous leukemia cell lines. Drug Des Devel Ther. 11:1115–1126. 2017. View Article : Google Scholar | |
Elzinga BM, Nyhan MJ, Crowley LC, O'Donovan TR, Cahill MR and McKenna SL: Induction of autophagy by Imatinib sequesters Bcr-Abl in autophagosomes and down-regulates Bcr-Abl protein. Am J Hematol. 88:455–462. 2013. View Article : Google Scholar | |
Zhu S, Cao L, Yu Y, Yang L, Yang M, Liu K, Huang J, Kang R, Livesey KM and Tang D: Inhibiting autophagy potentiates the anticancer activity of IFN1@/IFNα in chronic myeloid leukemia cells. Autophagy. 9:317–327. 2013. View Article : Google Scholar | |
Bosnjak M, Ristic B, Arsikin K, Mircic A, Suzin-Zivkovic V, Perovic V, Bogdanovic A, Paunovic V, Markovic I, Bumbasirevic V, et al: Inhibition of mTOR-dependent autophagy sensitizes leukemic cells to cytarabine-induced apoptotic death. PLoS One. 9:e943742014. View Article : Google Scholar | |
Pan Y, Gao Y, Chen L, Gao G, Dong H, Yang Y, Dong B and Chen X: Targeting autophagy augments in vitro and in vivo antimyeloma activity of DNA-damaging chemotherapy. Clin Cancer Res. 17:3248–3258. 2011. View Article : Google Scholar | |
Wang Z, Zhu S, Zhang G and Liu S: Inhibition of autophagy enhances the anticancer activity of bortezomib in B-cell acute lymphoblastic leukemia cells. Am J Cancer Res. 5:639–650. 2015. | |
Granato M, Santarelli R, Lotti LV, Di Renzo L, Gonnella R, Garufi A, Trivedi P, Frati L, D'Orazi G, Faggioni A, et al: JNK and macroautophagy activation by bortezomib has a pro-survival effect in primary effusion lymphoma cells. PLoS One. 8:e759652013. View Article : Google Scholar | |
Han W, Sun J, Feng L, Wang K, Li D, Pan Q, Chen Y, Jin W, Wang X, Pan H, et al: Autophagy inhibition enhances daunorubicin-induced apoptosis in K562 cells. PLoS One. 6:e284912011. View Article : Google Scholar | |
Marignac Martinez VL, Smith S, Toban N, Bazile M and Aloyz R: Resistance to Dasatinib in primary chronic lymphocytic leukemia lymphocytes involves AMPK-mediated energetic re-programming. Oncotarget. 4:2550–2566. 2013. | |
Morita M, Nishinaka Y, Kato I, Saida S, Hiramatsu H, Kamikubo Y, Heike T, Nakahata T and Adachi S: Dasatinib induces autophagy in mice with Bcr-Abl-positive leukemia. Int J Hematol. 105:335–340. 2017. View Article : Google Scholar | |
Kharaziha P, De Raeve H, Fristedt C, Li Q, Gruber A, Johnsson P, Kokaraki G, Panzar M, Laane E, Osterborg A, et al: Sorafenib has potent antitumor activity against multiple myeloma in vitro, ex vivo, and in vivo in the 5T33MM mouse model. Cancer Res. 72:5348–5362. 2012. View Article : Google Scholar | |
Takahashi H, Inoue J, Sakaguchi K, Takagi M, Mizutani S and Inazawa J: Autophagy is required for cell survival under L-asparaginase-induced metabolic stress in acute lymphoblastic leukemia cells. Oncogene. 36:4267–4276. 2017. View Article : Google Scholar | |
Schnekenburger M, Grandjenette C, Ghelfi J, Karius T, Foliguet B, Dicato M and Diederich M: Sustained exposure to the DNA demethylating agent, 2-deoxy-5-azacytidine, leads to apoptotic cell death in chronic myeloid leukemia by promoting differentiation, senescence, and autophagy. Biochem Pharmacol. 81:364–378. 2011. View Article : Google Scholar | |
Romano A, Giallongo C, La Cava P, Parrinello NL, Chiechi A, Vetro C, Tibullo D, Di Raimondo F, Liotta LA, Espina V, et al: Proteomic analysis reveals autophagy as pro-survival pathway elicited by long-term exposure with 5-azacitidine in high-risk myelodysplasia. Front Pharmacol. 8:2042017. View Article : Google Scholar | |
Evangelisti C, Evangelisti C, Chiarini F, Lonetti A, Buontempo F, Neri LM, McCubrey JA and Martelli AM: Autophagy in acute leukemias: A double-edged sword with important therapeutic implications. Biochim Biophys Acta. 1853:14–26. 2015. View Article : Google Scholar | |
Ekiz HA, Can G and Baran Y: Role of autophagy in the progression and suppression of leukemias. Crit Rev Oncol Hematol. 81:275–285. 2012. View Article : Google Scholar |