Autophagy and Its Research Progress in Gastric Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 YUZhao-yan , WANGRun-hua ,  ZHANGZhong-min

Department of General Surgery, People's Hospital of Guizhou Province, Guiyang 550002, Guizhou Province, China;

Corresponding author：

ZHANGZhong-min, Email: 382389687@qq.com

Keywords：

Gastric cancer; Autophagy; Autophagy-related gene; Microtubule-associated protein 1 light chain 3; Beclin 1 gene

DOI：

10.7507/1007-9424.20150033

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To summarize the autophagy and its research progress in gastric cancer. Methods In combination with available literatures published in recent years involving the relationship between autophagy and gastric cancer, the characteristics of autophagy, molecular marker, control factors, and the significance and role in gastric cancer were reviewed. Results Autophagy not only promotes cell death, but also can prolong the survival of cancer cells during the tumor formation. Reagents (including traditional Chinese medicine) regulating autophagy have broad prospect of application in cancer therapy, but anti-tumor therapeutic effect based on the regulation of autophagy depends on the actual level of intracellular autophagy. Conclusion The autophagy in the gastric cancer is still poorly understood, and to clarify the molecular mechanism of autophagy and kill cancer cells by reasonable regulation of autophagy still needs more further in-depth studies.

Citation： YUZhao-yan, WANGRun-hua, ZHANGZhong-min. Autophagy and Its Research Progress in Gastric Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(1): 121-125. doi: 10.7507/1007-9424.20150033 Copy

1.	Hartgrink HH, Jansen EP, van Grieken NC, et al.Gastric cancer.Lancet, 2009, 374(9688):477-490.
2.	Brenner H, Rothenbacher D, Arndt V.Epidemiology of stomach cancer.Methods Mol Biol, 2009, 472(11):467-477.
3.	He LQ, Lu JH, Yue ZY.Autophagy in ageing and ageing-associated diseases.Acta Pharmacol Sin, 2013, 34(5):605-611.
4.	Gozuacik D, Kimchi A.Autophagy as a cell death and tumor suppressor mechanism.Oncogene, 2004, 23(16):2891-2906.
5.	Ye MX, Li Y, Yin H, et al.Curcumin:updated molecular mechanisms and intervention targets in human lung cancer.Int J Mol Sci, 2012, 13(3):3959-3978.
6.	Lum JJ, DeBerardinis RJ, Thompson CB.Autophagy in metazoans:cell survival in the land of plenty.Nat Rev Mol Cell Biol, 2005, 6(6):439-448.
7.	Itakura E, Mizushima N.Characterization of autophagosome formation site by a hierarchical analysis of mammalian Atg proteins.Autophagy, 2010, 6(6):764-776.
8.	Ravikumar B, Sarkar S, Davies JE, et al.Regulation of mammalian autophagy in physiology and pathophysiology.Physiol Rev, 2010, 90(4):1383-1435.
9.	Kabeya Y, Mizushima N, Ueno T, et al.LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.EMBO J, 2000, 19(21):5720-5728.
10.	Liang XH, Yu J, Brown K, et al.Beclin 1 contains a leucine-rich nuclear export signal that is required for its autophagy and tumor suppressor function.Cancer Res, 2001, 61(8):3443-3449.
11.	Wei SH, Li W, Liu Y, et al.Disturbance of autophagy-lysosome signaling molecule expression in human gastric adenocarcinoma.Oncol Lett, 2014, 7(3):635-640.
12.	Kang R, Zeh HJ, Lotze MT, et al.The Beclin 1 network regulates autophagy and apoptosis.Cell Death Differ, 2011, 18(4):571-580.
13.	Pattingre S, Tassa A, Qu X, et al.Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy.Cell, 2005, 122(6):927-939.
14.	Pankiv S, Clausen TH, Lamark T, et al.p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy.J Biol Chem, 2007, 282(33):24131-24145.
15.	Mathew R, Kongara S, Beaudoin B, et al.Autophagy suppresses tumor progression by limiting chromosomal instability.Genes Dev, 2007, 21(11):1367-1381.
16.	Mathew R, Karp CM, Beaudoin B, et al.Autophagy suppresses tumorigenesis through elimination of p6.Cell, 2009, 137(6):1062-1075.
17.	Wu WK, Coffelt SB, Cho CH, et al.The autophagic paradox in cancer therapy.Oncogene, 2012, 31(8):939-953.
18.	Geng QR, Xu DZ, He LJ, et al.Beclin-1 expression is a significant predictor of survival in patients with lymph node-positive gastric cancer.PLoS One, 2012, 7(9):e45968.
19.	Chen YB, Hou JH, Feng XY, et al.Decreased expression of Beclin 1 correlates with a metastatic phenotypic feature and adverse prognosis of gastric carcinomas.J Surg Oncol, 2012, 105(6):542-547.
20.	郭长青, 邵经浩, 卢瑞利, 等.胃癌组织中Beclin 1和PTEN蛋白的表达.郑州大学学报:医学版, 2010, 45(3):463-466.
21.	马陆军, 林瑶光.S100A11和自噬基因Beclin1在胃癌组织中的表达及临床意义.世界华人消化杂志, 2012, 20(33):3266-3271.
22.	Wang HB, Zhou CJ, Song SZ, et al.Evaluation of Nrf2 and IGF-1 expression in benign, premalignant and malignant gastric lesions.Pathol Res Pract, 2011, 207(3):169-173.
23.	Faried LS, Faried A, Kanuma T, et al.Expression of an activated mammalian target of rapamycin in adenocarcinoma of the cervix:A potential biomarker and molecular target therapy.Mol Carcinog, 2008, 47(6):446-457.
24.	Mehrpour M, Esclatine A, Beau I, et al.Overview of macroautophagy regulation in mammalian cells.Cell Res, 2010, 20(7):748-746.
25.	Kim HS, Han HD, Armaiz-Pena GN, et al.Functional roles of Src and Fgr in ovarian carcinoma.Clin Cancer Res, 2011, 17(7):1713-1721.
26.	Zhu BS, Yu LY, Zhao K, et al.Effects of small interfering RNA inhibit Class I phosphoinositide 3-kinase on human gastric cancer cells.World J Gastroenterol, 2013, 19(11):1760-1769.
27.	徐玲, 曲秀娟, 刘云鹏, 等.保护性自噬对5-FU诱导的胃癌细胞凋亡的抑制作用.世界华人消化杂志, 2011, 19(8):777-781.
28.	Cecconi F.Autophagy regulation by miRNAs:when cleaning goes out of service.EMBO J, 2011, 30(11):4517-4519.
29.	Jung CH, Ro SH, Cao J, et al.mTOR regulation of autophagy.FEBS Lett, 2010, 584(7):1287-1295.
30.	Alexander A, Cai SL, Kim J, et al.ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS.Proc Natl Acad Sci, 2010, 107(9):4153-4158.
31.	Ji D, Zhang Z, Cheng L, et al.The combination of RAD001 and MK-2206 exerts synergistic cytotoxic effects against PTEN mutant gastric cancer cells:involvement of MAPK-dependent autophagic, but not apoptotic cell death pathway.PLoS One, 2014, 9(1):e85116.
32.	Zhu BS, Xing CG, Lin F, et al.Blocking NF-κB nuclear translocation leads to p53-related autophagy activation and cell apoptosis.World J Gastroenterol, 2011, 17(4):478-487.
33.	Xie B, Zhou J, Shu G, et al.Restoration of klotho gene expression induces apoptosis and autophagy in gastric cancer cells:tumor suppressive role of klotho in gastric cancer.Cancer Cell Int, 2013, 13(1):18-27.
34.	Claerhout S, Lim JY, Choi W, et al.Gene expression signature analysis identifies vorinostat as a candidate therapy for gastric cancer.PLoS One, 2011, 6(9):e2466.
35.	Zhu H, Wu H, Liu X, et al.Regulation of autophagy by a beclin 1-targeted microRNA, miR-30a, in cancer cells.Autophagy, 2009, 5(6):816-823.
36.	Korkmaz G, le Sage C, Tekirdag KA, et al.miR-376b controls starvation and mTOR inhibition-related autophagy by targeting ATG4C and BECN1.Autophagy, 2012, 8(2):165-176.
37.	Frankel LB, Wen J, Lees M, et al.microRNA-101 is a potent inhibitor of autophagy.EMBO J, 2011, 30(22):4628-4641.
38.	Wan G, Xie W, Liu Z, et al.Hypoxia-induced MIR155 is a potent autophagy inducer by targeting multiple players in the MTOR pathway.Autophagy, 2014, 10(1):70-79.
39.	Hu YL, DeLay M, Jahangiri A, et al.Hypoxia-induced autophagy promotes tumor cell survival and adaptation to antiangiogenic treatment in glioblastoma.Cancer Res, 2012, 72(7):1773-1783.
40.	Peracchio C, Alabiso O, Valente G, et al.Involvement of autophagy in ovarian cancer:a working hypothesis.J Ovarian Res, 2012, 5(6):22-31.
41.	Xu L, Qu XJ, Liu YP, et al.Protective autophagy antagonizes oxaliplatin-induced apoptosis in gastric cancer cells.Chin J Cancer, 2011, 30(7):490-496.
42.	Steeves MA, Dorsey FC, Cleveland JL.Targeting the autophagy pathway for cancer chemoprevention.Curr Opin Cell Biol, 2010, 22(2):218-225.
43.	Levy JM, Thorburn A.Targeting autophagy during cancer therapy to improve clinical outcomes.Pharmacol Ther, 2011, 131(1):130-141.
44.	Ogata A, Yanagie H, Ishikawa E, et al.Antitumour effect of polyoxomolybdates:induction of apoptotic cell death and autophagy in in vitro and in vivo models.Br J Cancer, 2008, 98(2):399-409.
45.	Liang C, Li H, Zhou H, et al.Recombinant Lz-8 from Ganoderma lucidum induces endoplasmic reticulum stress-mediated autophagic cell death in SGC-7901 human gastric cancer cells.Oncol Rep, 2012, 27(4):1079-1089.
46.	46张晔, 赵明芳, 刘云鹏, 等.蟾蜍灵诱导人胃癌SGC7901细胞自噬与凋亡的研究.现代肿瘤医学, 2013, 21(10):2155-2157.
47.	赵雪峰, 魏敬妙, 李勇, 等.丹参酮ⅡA诱导体外胃癌细胞的自噬.中成药, 2014, 36(1):10-14.
48.	王红钰, 王爱军, 郑宝军, 等.二氢青蒿素诱导胃癌SGC7901细胞体外自噬研究.广东医学, 2012, 33(22):3394-3397.
49.	Liu J, Zhang Y, Qu J, et al.β-Elemene-induced autophagy protects human gastric cancer cells from undergoing apoptosis.BMC Cancer, 2011, 11(4):183-192.
50.	Rasul A, Yu B, Khan M, et al.Magnolol, a natural compound, induces apoptosis of SGC-7901 human gastric adenocarcinoma cells via the mitochondrial and PI3K/Akt signaling pathways.Int J Oncol, 2012, 40(4):1153-1161.
51.	Wojtkowiak JW, Rothberg JM, Kumar V, et al.Chronic autophagy is a cellular adaptation to tumor acidic pH microenvironments.Cancer Res, 2012, 72(16):3938-3947.

1. Hartgrink HH, Jansen EP, van Grieken NC, et al.Gastric cancer.Lancet, 2009, 374(9688):477-490.
2. Brenner H, Rothenbacher D, Arndt V.Epidemiology of stomach cancer.Methods Mol Biol, 2009, 472(11):467-477.
3. He LQ, Lu JH, Yue ZY.Autophagy in ageing and ageing-associated diseases.Acta Pharmacol Sin, 2013, 34(5):605-611.
4. Gozuacik D, Kimchi A.Autophagy as a cell death and tumor suppressor mechanism.Oncogene, 2004, 23(16):2891-2906.
5. Ye MX, Li Y, Yin H, et al.Curcumin:updated molecular mechanisms and intervention targets in human lung cancer.Int J Mol Sci, 2012, 13(3):3959-3978.
6. Lum JJ, DeBerardinis RJ, Thompson CB.Autophagy in metazoans:cell survival in the land of plenty.Nat Rev Mol Cell Biol, 2005, 6(6):439-448.
7. Itakura E, Mizushima N.Characterization of autophagosome formation site by a hierarchical analysis of mammalian Atg proteins.Autophagy, 2010, 6(6):764-776.
8. Ravikumar B, Sarkar S, Davies JE, et al.Regulation of mammalian autophagy in physiology and pathophysiology.Physiol Rev, 2010, 90(4):1383-1435.
9. Kabeya Y, Mizushima N, Ueno T, et al.LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.EMBO J, 2000, 19(21):5720-5728.
10. Liang XH, Yu J, Brown K, et al.Beclin 1 contains a leucine-rich nuclear export signal that is required for its autophagy and tumor suppressor function.Cancer Res, 2001, 61(8):3443-3449.
11. Wei SH, Li W, Liu Y, et al.Disturbance of autophagy-lysosome signaling molecule expression in human gastric adenocarcinoma.Oncol Lett, 2014, 7(3):635-640.
12. Kang R, Zeh HJ, Lotze MT, et al.The Beclin 1 network regulates autophagy and apoptosis.Cell Death Differ, 2011, 18(4):571-580.
13. Pattingre S, Tassa A, Qu X, et al.Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy.Cell, 2005, 122(6):927-939.
14. Pankiv S, Clausen TH, Lamark T, et al.p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy.J Biol Chem, 2007, 282(33):24131-24145.
15. Mathew R, Kongara S, Beaudoin B, et al.Autophagy suppresses tumor progression by limiting chromosomal instability.Genes Dev, 2007, 21(11):1367-1381.
16. Mathew R, Karp CM, Beaudoin B, et al.Autophagy suppresses tumorigenesis through elimination of p6.Cell, 2009, 137(6):1062-1075.
17. Wu WK, Coffelt SB, Cho CH, et al.The autophagic paradox in cancer therapy.Oncogene, 2012, 31(8):939-953.
18. Geng QR, Xu DZ, He LJ, et al.Beclin-1 expression is a significant predictor of survival in patients with lymph node-positive gastric cancer.PLoS One, 2012, 7(9):e45968.
19. Chen YB, Hou JH, Feng XY, et al.Decreased expression of Beclin 1 correlates with a metastatic phenotypic feature and adverse prognosis of gastric carcinomas.J Surg Oncol, 2012, 105(6):542-547.
20. 郭长青, 邵经浩, 卢瑞利, 等.胃癌组织中Beclin 1和PTEN蛋白的表达.郑州大学学报:医学版, 2010, 45(3):463-466.
21. 马陆军, 林瑶光.S100A11和自噬基因Beclin1在胃癌组织中的表达及临床意义.世界华人消化杂志, 2012, 20(33):3266-3271.
22. Wang HB, Zhou CJ, Song SZ, et al.Evaluation of Nrf2 and IGF-1 expression in benign, premalignant and malignant gastric lesions.Pathol Res Pract, 2011, 207(3):169-173.
23. Faried LS, Faried A, Kanuma T, et al.Expression of an activated mammalian target of rapamycin in adenocarcinoma of the cervix:A potential biomarker and molecular target therapy.Mol Carcinog, 2008, 47(6):446-457.
24. Mehrpour M, Esclatine A, Beau I, et al.Overview of macroautophagy regulation in mammalian cells.Cell Res, 2010, 20(7):748-746.
25. Kim HS, Han HD, Armaiz-Pena GN, et al.Functional roles of Src and Fgr in ovarian carcinoma.Clin Cancer Res, 2011, 17(7):1713-1721.
26. Zhu BS, Yu LY, Zhao K, et al.Effects of small interfering RNA inhibit Class I phosphoinositide 3-kinase on human gastric cancer cells.World J Gastroenterol, 2013, 19(11):1760-1769.
27. 徐玲, 曲秀娟, 刘云鹏, 等.保护性自噬对5-FU诱导的胃癌细胞凋亡的抑制作用.世界华人消化杂志, 2011, 19(8):777-781.
28. Cecconi F.Autophagy regulation by miRNAs:when cleaning goes out of service.EMBO J, 2011, 30(11):4517-4519.
29. Jung CH, Ro SH, Cao J, et al.mTOR regulation of autophagy.FEBS Lett, 2010, 584(7):1287-1295.
30. Alexander A, Cai SL, Kim J, et al.ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS.Proc Natl Acad Sci, 2010, 107(9):4153-4158.
31. Ji D, Zhang Z, Cheng L, et al.The combination of RAD001 and MK-2206 exerts synergistic cytotoxic effects against PTEN mutant gastric cancer cells:involvement of MAPK-dependent autophagic, but not apoptotic cell death pathway.PLoS One, 2014, 9(1):e85116.
32. Zhu BS, Xing CG, Lin F, et al.Blocking NF-κB nuclear translocation leads to p53-related autophagy activation and cell apoptosis.World J Gastroenterol, 2011, 17(4):478-487.
33. Xie B, Zhou J, Shu G, et al.Restoration of klotho gene expression induces apoptosis and autophagy in gastric cancer cells:tumor suppressive role of klotho in gastric cancer.Cancer Cell Int, 2013, 13(1):18-27.
34. Claerhout S, Lim JY, Choi W, et al.Gene expression signature analysis identifies vorinostat as a candidate therapy for gastric cancer.PLoS One, 2011, 6(9):e2466.
35. Zhu H, Wu H, Liu X, et al.Regulation of autophagy by a beclin 1-targeted microRNA, miR-30a, in cancer cells.Autophagy, 2009, 5(6):816-823.
36. Korkmaz G, le Sage C, Tekirdag KA, et al.miR-376b controls starvation and mTOR inhibition-related autophagy by targeting ATG4C and BECN1.Autophagy, 2012, 8(2):165-176.
37. Frankel LB, Wen J, Lees M, et al.microRNA-101 is a potent inhibitor of autophagy.EMBO J, 2011, 30(22):4628-4641.
38. Wan G, Xie W, Liu Z, et al.Hypoxia-induced MIR155 is a potent autophagy inducer by targeting multiple players in the MTOR pathway.Autophagy, 2014, 10(1):70-79.
39. Hu YL, DeLay M, Jahangiri A, et al.Hypoxia-induced autophagy promotes tumor cell survival and adaptation to antiangiogenic treatment in glioblastoma.Cancer Res, 2012, 72(7):1773-1783.
40. Peracchio C, Alabiso O, Valente G, et al.Involvement of autophagy in ovarian cancer:a working hypothesis.J Ovarian Res, 2012, 5(6):22-31.
41. Xu L, Qu XJ, Liu YP, et al.Protective autophagy antagonizes oxaliplatin-induced apoptosis in gastric cancer cells.Chin J Cancer, 2011, 30(7):490-496.
42. Steeves MA, Dorsey FC, Cleveland JL.Targeting the autophagy pathway for cancer chemoprevention.Curr Opin Cell Biol, 2010, 22(2):218-225.
43. Levy JM, Thorburn A.Targeting autophagy during cancer therapy to improve clinical outcomes.Pharmacol Ther, 2011, 131(1):130-141.
44. Ogata A, Yanagie H, Ishikawa E, et al.Antitumour effect of polyoxomolybdates:induction of apoptotic cell death and autophagy in in vitro and in vivo models.Br J Cancer, 2008, 98(2):399-409.
45. Liang C, Li H, Zhou H, et al.Recombinant Lz-8 from Ganoderma lucidum induces endoplasmic reticulum stress-mediated autophagic cell death in SGC-7901 human gastric cancer cells.Oncol Rep, 2012, 27(4):1079-1089.
46. 46张晔, 赵明芳, 刘云鹏, 等.蟾蜍灵诱导人胃癌SGC7901细胞自噬与凋亡的研究.现代肿瘤医学, 2013, 21(10):2155-2157.
47. 赵雪峰, 魏敬妙, 李勇, 等.丹参酮ⅡA诱导体外胃癌细胞的自噬.中成药, 2014, 36(1):10-14.
48. 王红钰, 王爱军, 郑宝军, 等.二氢青蒿素诱导胃癌SGC7901细胞体外自噬研究.广东医学, 2012, 33(22):3394-3397.
49. Liu J, Zhang Y, Qu J, et al.β-Elemene-induced autophagy protects human gastric cancer cells from undergoing apoptosis.BMC Cancer, 2011, 11(4):183-192.
50. Rasul A, Yu B, Khan M, et al.Magnolol, a natural compound, induces apoptosis of SGC-7901 human gastric adenocarcinoma cells via the mitochondrial and PI3K/Akt signaling pathways.Int J Oncol, 2012, 40(4):1153-1161.
51. Wojtkowiak JW, Rothberg JM, Kumar V, et al.Chronic autophagy is a cellular adaptation to tumor acidic pH microenvironments.Cancer Res, 2012, 72(16):3938-3947.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Autophagy and Its Research Progress in Gastric Cancer

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