药学学报, 2016, 51(1): 23-28
引用本文:
刘虹, 邵荣光. 自噬在肿瘤发生与发展过程中的调节作用[J]. 药学学报, 2016, 51(1): 23-28.
LIU Hong, SHAO Rong-guang. The regulatory role of autophagy in tumor process[J]. Acta Pharmaceutica Sinica, 2016, 51(1): 23-28.

自噬在肿瘤发生与发展过程中的调节作用
刘虹, 邵荣光
中国医学科学院、北京协和医学院医药生物技术研究所, 北京 100050
摘要:
自噬是经典的细胞内能量代谢和自我更新机制, 在生物发育和维持机体稳态过程中发挥重要作用。近年来的大量研究表明自噬与肿瘤密切相关, 自噬可以调节肿瘤的形成、增殖、转移以及能量代谢等诸多方面。同时, 以调节自噬活性为理论依据的抗肿瘤药物已应用于临床治疗, 通过改善自噬活性而抑制肿瘤已经成为肿瘤治疗的新思路。本文总结概述了近年来自噬相关的调节机制、自噬与肿瘤的关系及其在肿瘤治疗中的应用。
关键词:    自噬      肿瘤      肿瘤治疗     
The regulatory role of autophagy in tumor process
LIU Hong, SHAO Rong-guang
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Abstract:
Autophagy is a classical regulatory mechanism of energy metabolism and self-update system in the maintenance of the intracellular homeostasis and cell development. Autophagy has been recently found to play a role in tumor development. Autophagy regulates tumor formation, proliferation, metastasis, and metabolism. At the same time, the anticancer drugs formed with autophagic mediators have been used in the treatment, which suggested that improving autophagy activity to inhibit tumor has become a new way for cancer treatment of cancer patients. This article gives an overview of the regulatory mechanism of autophagy, the relationship between autophagy and tumor, and tumor therapy by targeting autophagy.
Key words:    autophagy    tumor    tumor therapy   
收稿日期: 2015-09-16
DOI: 10.16438/j.0513-4870.2015-0809
基金项目: 国家自然科学基金资助项目 (31401186, 81473249); 国家“重大新药创制”科技重大专项资助项目 (2014ZX09201042)
通讯作者: 邵荣光
Email: shaor@imb.pumc.edu.cn
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参考文献:
[1] Mathew R, Karp CM, Beaudoin B, et al. Autophagy suppresses tumorigenesis through elimination of p62 [J]. Cell, 2009, 137: 1062-1075.
[2] Rabinowitz JD, White E. Autophagy and metabolism [J]. Science, 2010, 330: 1344-1348.
[3] Singh R, Kaushik S, Wang Y, et al. Autophagy regulates lipid metabolism [J]. Nature, 2009, 458: 1131-1135.
[4] Liu B, Bao JK, Yang JM, et al. Targeting autophagic pathways for cancer drug discovery [J]. Chin J Cancer, 2013, 32: 113-120.
[5] Bhattacharya A, Wei Q, Shin JN, et al. Autophagy is required for neutrophil-mediated inflammation [J]. Cell Rep, 2015, 12: 1731-1739.
[6] Budanov AV, Karin M. p53 target genes sestrin1 and sestrin 2 connect genotoxic stress and mTOR signaling [J]. Cell, 2008, 134: 451-460.
[7] Li Q, Ren J. Chronic alcohol consumption alters mammalian target of rapamycin (mTOR), reduces ribosomal p70s6 kinase and p4E-BP1 levels in mouse cerebral cortex [J]. Exp Neurol, 2007, 204: 840-844.
[8] Kim YC, Guan KL. mTOR: a pharmacologic target for autophagy regulation [J]. J Clin Invest, 2015, 125: 25-32.
[9] Jung CH, Ro SH, Cao J, et al. mTOR regulation of autophagy [J]. FEBS Lett, 2010, 584: 1287-1295.
[10] Kim J, Kundu M, Viollet B, et al. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1 [J]. Nat Cell Biol, 2011, 13: 132-141.
[11] Liu H, Mi S, Li Z, et al. Interleukin 17A inhibits autophagy through activation of PIK3CA to interrupt the GSK3B- mediated degradation of BCL2 in lung epithelial cells [J]. Autophagy, 2013, 9: 730-742.
[12] Zalckvar E, Berissi H, Eisenstein M, et al. Phosphorylation of Beclin 1 by DAP-kinase promotes autophagy by weakening its interactions with Bcl-2 and Bcl-XL [J]. Autophagy, 2009, 5: 720-722.
[13] Kang R, Livesey KM, Zeh HJ, et al. HMGB1: a novel Beclin 1- binding protein active in autophagy [J]. Autophagy, 2010, 6: 1209-1211.
[14] Zhu X, Messer JS, Wang Y, et al. Cytosolic HMGB1 controls the cellular autophagy/apoptosis checkpoint during inflammation [J]. J Clin Invest, 2015, 125: 1098-1110.
[15] Molejon MI, Ropolo A, Re AL, et al. The VMP1-Beclin 1 interaction regulates autophagy induction [J]. Sci Rep, 2013, 3: 1055.
[16] Ueno S, Ueno T, Iwao Y. Role of the PI3K-TOR-S6K pathway in the onset of cell cycle elongation during Xenopus early embryogenesis [J]. Dev Growth Differ, 2011, 53: 924- 933.
[17] Funderburk SF, Wang QJ, Yue Z. The Beclin 1-VPS34 complex--at the crossroads of autophagy and beyond [J]. Trends Cell Biol, 2010, 20: 355-362.
[18] Otomo C, Metlagel Z, Takaesu G, et al. Structure of the human ATG12-ATG5 conjugate required for LC3 lipidation in autophagy [J]. Nat Struct Mol Biol, 2013, 20: 59-66.
[19] Martinez J, Malireddi RK, Lu Q, et al. Molecular characteri­zation of LC3-associated phagocytosis reveals distinct roles for Rubicon, NOX2 and autophagy proteins [J]. Nat Cell Biol, 2015, 17: 893-906.
[20] Kroemer G, Jäättelä M. Lysosomes and autophagy in cell death control [J]. Nat Rev Cancer, 2005, 5: 886-897.
[21] Ganley IG, Wong PM, Gammoh N, et al. Distinct auto­phagosomal-lysosomal fusion mechanism revealed by thapsi­gargin-induced autophagy arrest [J]. Mol Cell, 2011, 42: 731-743.
[22] Moreau K, Renna M, Rubinsztein DC. Connections between SNAREs and autophagy [J]. Trends Biochem Sci, 2013, 38: 57-63.
[23] Fu LL, Cheng Y, Liu B. Beclin-1: autophagic regulator and therapeutic target in cancer [J]. Int J Biochem Cell Biol, 2013, 45: 921-924.
[24] Liang XH, Jackson S, Seaman M, et al. Induction of auto­phagy and inhibition of tumorigenesis by Beclin 1 [J]. Nature, 1999, 402: 672-676.
[25] White E. The role for autophagy in cancer [J]. J Clin Invest, 2015, 125: 42-46.
[26] Degenhardt K, Mathew R, Beaudoin B, et al. Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis [J]. Cancer Cell, 2006, 10: 51-64.
[27] Karantza-Wadsworth V, Patel S, Kravchuk O, et al. Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis [J]. Genes Dev, 2007, 21: 1621-1635.
[28] Kongara S, Kravchuk O, Teplova I, et al. Autophagy regulates keratin 8 homeostasis in mammary epithelial cells and in breast tumors [J]. Mol Cancer Res, 2010, 8: 873-884.
[29] Mathew R, Kongara S, Beaudoin B, et al. Autophagy suppresses tumor progression by limiting chromosomal instability [J]. Genes Dev, 2007, 21: 1367-1381.
[30] Hait WN, Jin S, Yang JM. A matter of life or death (or both): understanding autophagy in cancer [J]. Clin Cancer Res, 2006, 12: 1961-1965.
[31] Kenific CM, Thorburn A, Debnath J. Autophagy and metas­tasis: another double-edged sword [J]. Curr Opin Cell Biol, 2010, 22: 241-245.
[32] Lv Q, Wang W, Xue J, et al. DEDD interacts with PI3KC3 to activate autophagy and attenuate epithelial-mesenchymal transition in human breast cancer [J]. Cancer Res, 2012, 72: 3238-3250.
[33] Ueno T, Sato W, Horie Y, et al. Loss of PTEN, a tumor suppressor, causes the strong inhibition of autophagy without affecting LC3 lipidation [J]. Autophagy, 2008, 4: 692-700.
[34] Arico S, Petiot A, Bauvy C, et al. The tumor suppressor PTEN positively regulates macroautophagy by inhibiting the phosphatidylinositol 3-kinase/protein kinase B pathway [J]. J Biol Chem, 2001, 276: 35243-35246.
[35] Kittipongdaja W, Wu X, Garner J, et al. Rapamycin suppresses tumor growth and alters the metabolic phenotype in T-cell lymphoma [J]. J Invest Dermatol, 2015, 135: 2301-2308.
[36] Tasdemir E, Chiara Maiuri M, Morselli E, et al. A dual role of p53 in the control of autophagy [J]. Autophagy, 2008, 4: 810-814.
[37] Yao W, Feng D, Bian W, et al. EBP50 inhibits EGF-induced breast cancer cell proliferation by blocking EGFR phosphory­lation [J]. Amino Acids, 2012, 43: 2027-2035.
[38] Liu H, Ma Y, He HW, et al. SLC9A3R1 stimulates autophagy via BECN1 stabilization in breast cancer cells [J]. Autophagy, 2015. DOI: 10.1080/15548627.2015.1074372.
[39] Hu YL, DeLay M, Jahangiri A, et al. Hypoxia-induced auto­phagy promotes tumor cell survival and adaptation to antian­giogenic treatment in glioblastoma [J]. Cancer Res, 2012, 72: 1773-1783.
[40] Yang S, Wang X, Contino G, et al. Pancreatic cancers require autophagy for tumor growth [J]. Genes Dev, 2011, 25: 717- 729.
[41] Guo JY, Chen HY, Mathew R, et al. Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis [J]. Genes Dev, 2011, 25: 460-470.
[42] White E, Mehnert JM, Chan CS. Autophagy, metabolism, and cancer [J]. Clin Cancer Res, 2015, 21: 5037-5046.
[43] Yang A, Rajeshkumar NV, Wang X, et al. Autophagy is critical for pancreatic tumor growth and progression in tumors with p53 alterations [J]. Cancer Discov, 2014, 4: 905-913.
[44] Ballou LM, Lin RZ. Rapamycin and mTOR kinase inhibitors [J]. J Chem Biol, 2008, 1: 27-36.
[45] Meric-Bernstam F, Gonzalez-Angulo AM. Targeting the mTOR signaling network for cancer therapy [J]. J Clin Oncol, 2009, 27: 2278-2287.
[46] Qian W, Liu J, Jin J, et al. Arsenic trioxide induces not only apoptosis but also autophagic cell death in leukemia cell lines via up-regulation of Beclin-1 [J]. Leuk Res, 2007, 31: 329- 339.
[47] Yang ZJ, Chee CE, Huang S, et al. The role of autophagy in cancer: therapeutic implications [J]. Mol Cancer Ther, 2011, 10: 1533-1541.
[48] Li X, Xu HL, Liu YX, et al. Autophagy modulation as a target for anticancer drug discovery [J]. Acta Pharmacol Sin, 2013, 34: 612-624.
[49] Cerniglia GJ, Karar J, Tyagi S, et al. Inhibition of autophagy as a strategy to augment radiosensitization by the dual phos­phatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 [J]. Mol Pharmacol, 2012, 82: 1230- 1240.
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