自噬作用是一種高度保守的溶酶體介導的分解代謝過程，藉此降解受損的細胞器和蛋白質，在DNA修復中也扮演著重要角色。儘管自噬作用被認為是 DNA 損傷反應和DNA 修復的正向調控因子，但我們之前證明下調存活素透過小分子干擾核糖核酸和YM155（抑制存活素表達的臨床 II 期藥物）會上調自噬作用並誘導自噬依賴性 DNA 損傷和細胞死亡在MDA-MB-231、MCF-7和SK-Br-3人類乳腺癌細胞中。 再者，下調存活素在細胞中誘導自噬上調介導的活性氧化物質 (ROS) 積累和DNA修復的抑制。然而，這些現象背後的機制尚不清楚。本篇研究中，透過生物資訊分析，我們發現KEAP1、NRF2、SOD1（已知調節氧化壓力的蛋白質）和RAD51、ATRX（參與同源重組 DNA 修復的蛋白質）含有潛在的 LC3 相互作用區域(LIR)結構模組。此外，我們發現分離的自噬體中存在KEAP1、NRF2、SOD1、RAD51和ATRX，進一步表明這些蛋白質是潛在的自噬作用受質。有趣的是，存活素的下調降低了MDA-MB-231細胞中SOD1的酵素活性和KEAP1、NRF2、SOD1、RAD51和ATRX的蛋白質表達。此外，由BIRC5介導的這些蛋白質的下調透過自噬抑製劑CQ作用而減弱，這表明BIRC5是部分透過自噬作用調控這些蛋白質。我們還觀察到存活素的下調增加了LC3B或SQSTM1與這些蛋白質的相互作用，這可能有助於將蛋白質募集到自噬體中。在形態上，我們觀察到延長存活素小分子干擾核糖核酸的作用增加了DNA洩漏的細胞數量是透過自噬作用而非細胞凋亡。
總結我們的研究結果表明，自噬作用不一定是DNA損傷和基因組穩定性的正調節因子。在某些情況下，如存活素的下調，自噬作用的上調（或過度自噬）可引發DNA損傷以及造成基因組不穩定性，其部分源自於抗氧化蛋白和DNA修復相關蛋白的降解所造成。

Autophagy is a highly conserved lysosome-mediated catabolic process for the degradation of the damaged cellular organelles and proteins, and it also plays an important role in DNA repair. Despite the consensus of autophagy as a positive regulator of DNA damage response and DNA repair, we previously demonstrated that downregulation of BIRC5 by siRNA and YM155 (a clinical phase ll drug that inhibit BIRC5 expression) upregulated autophagy and induced autophagy-dependent DNA damage and cell death in MDA-MB-231, MCF-7 and SK-Br-3 human breast cancer cells. Moreover, downregulation of BIRC5 induced autophagy upregulation-mediated ROS accumulation and inhibition of DNA repair in cells. However, the mechanism underlying these phenomenon remains unclear. In the current study, through bioinformatic analysis, we found KEAP1, NRF2, SOD1 (proteins known to regulate oxidative stress) and RAD51, ATRX (proteins participate in homologous recombination DNA repair) contain potential LC3-interacting region (LIR) motifs. Moreover, we found the presence of KEAP1, NRF2, SOD1, RAD51 and ATRX in isolated autophagosomes, further suggesting that these proteins are potential autophagic substrates. Interestingly, downregulation of BIRC5 decreased the enzymatic activity of SOD1 and protein expression of KEAP1, NRF2, SOD1, RAD51 and ATR in MDA-MB-231 cells. Furthermore, the decrease of these protein mediated by BIRC5 downregulation was attenuated by co-incubation with the autophagy inhibitor, CQ. We also observed that downregulation of BIRC5 increased the interaction of LC3B or SQSTM1 with these proteins, which might contribute to recruit the proteins into autophagosome. Morphologically, we observed that prolonged treatment of BIRC5 siRNA increased the number of cells with DNA leakage through autophagy instead of apoptosis.
Collectively, our findings revealed that autophagy is not a definite DNA damage and genomic stability positive-regulator. Under certain circumstances, like BIRC5 downregulation, upregulation of autophagy (or excessive autophagy) can trigger DNA damage and to promote genomic instability in part through degradation of antioxidant proteins and DNA repair-involved proteins.

Alexander, A., Cai, S.-L., Kim, J., Nanez, A., Sahin, M., MacLean, K. H., . . . Person, M. D. (2010). ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS. Proceedings of the National Academy of Sciences, 107(9), 4153-4158.
Almacellas, E., Pelletier, J., Day, C., Ambrosio, S., Tauler, A., & Mauvezin, C. (2021). Lysosomal degradation ensures accurate chromosomal segregation to prevent chromosomal instability. Autophagy, 17(3), 796-813. doi:10.1080/15548627.2020.1764727
Altieri, D. C. (2008). Survivin, cancer networks and pathway-directed drug discovery. Nature Reviews Cancer, 8(1), 61-70. doi:10.1038/nrc2293
Ambrosini, G., Adida, C., & Altieri, D. C. (1997). A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nature medicine, 3(8), 917-921.
Basu, A. K. (2018). DNA Damage, Mutagenesis and Cancer. International Journal of Molecular Sciences, 19(4), 970. Retrieved from https://www.mdpi.com/1422-0067/19/4/970
Bekker-Jensen, S., Lukas, C., Kitagawa, R., Melander, F., Kastan, M. B., Bartek, J., & Lukas, J. (2006). Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks. J Cell Biol, 173(2), 195-206. doi:10.1083/jcb.200510130
Bellezza, I., Giambanco, I., Minelli, A., & Donato, R. (2018). Nrf2-Keap1 signaling in oxidative and reductive stress. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1865(5), 721-733.
Birgisdottir, Å. B., Lamark, T., & Johansen, T. (2013). The LIR motif–crucial for selective autophagy. Journal of cell science, 126(15), 3237-3247.
Bolton, M. A., Lan, W., Powers, S. E., McCleland, M. L., Kuang, J., & Stukenberg, P. T. (2002). Aurora B kinase exists in a complex with survivin and INCENP and its kinase activity is stimulated by survivin binding and phosphorylation. Molecular biology of the cell, 13(9), 3064-3077.
Burma, S., Chen, B. P., Murphy, M., Kurimasa, A., & Chen, D. J. (2001). ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J Biol Chem, 276(45), 42462-42467. doi:10.1074/jbc.C100466200
Cai, M., Hu, Z., Liu, J., Gao, J., Liu, C., Liu, D., . . . Lin, B. (2014). Beclin 1 expression in ovarian tissues and its effects on ovarian cancer prognosis. Int J Mol Sci, 15(4), 5292-5303. doi:10.3390/ijms15045292
Chakarov, S., Petkova, R., Russev, G. C., & Zhelev, N. (2014). DNA damage and mutation. Types of DNA damage. BioDiscovery, 11. doi:10.7750/BioDiscovery.2014.11.1
Changou, C. A., Chen, Y.-R., Xing, L., Yen, Y., Chuang, F. Y., Cheng, R. H., . . . Kung, H.-J. (2014). Arginine starvation-associated atypical cellular death involves mitochondrial dysfunction, nuclear DNA leakage, and chromatin autophagy. Proceedings of the National Academy of Sciences, 111(39), 14147-14152.
Chen, J., Zhang, Z., & Cai, L. (2014). Diabetic cardiomyopathy and its prevention by nrf2: current status. Diabetes Metab J, 38(5), 337-345. doi:10.4093/dmj.2014.38.5.337
Chen, J., Zhang, Z., & Cai, L. (2014). Diabetic Cardiomyopathy and Its Prevention by Nrf2: Current Status. Diabetes & metabolism journal, 38, 337-345. doi:10.4093/dmj.2014.38.5.337
Cheng, S. M., Lin, T. Y., Chang, Y. C., Lin, I. W., Leung, E., & Cheung, C. H. A. (2021). YM155 and BIRC5 downregulation induce genomic instability via autophagy-mediated ROS production and inhibition in DNA repair. Pharmacol Res, 166, 105474. doi:10.1016/j.phrs.2021.105474
Cheung, C. H. A., Huang, C.-C., Tsai, F.-Y., Lee, J. Y.-C., Cheng, S. M., Chang, Y.-C., . . . Chang, J.-Y. (2013). Survivin–biology and potential as a therapeutic target in oncology. OncoTargets and therapy, 6, 1453.
DeNicola, G. M., Karreth, F. A., Humpton, T. J., Gopinathan, A., Wei, C., Frese, K., . . . Tuveson, D. A. (2011). Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature, 475(7354), 106-109. doi:10.1038/nature10189
Deveraux, Q. L., & Reed, J. C. (1999). IAP family proteins—suppressors of apoptosis. Genes & development, 13(3), 239-252.
Dhillon, H., Chikara, S., & Reindl, K. M. (2014). Piperlongumine induces pancreatic cancer cell death by enhancing reactive oxygen species and DNA damage. Toxicology reports, 1, 309-318. doi:https://doi.org/10.1016/j.toxrep.2014.05.011
Durand, N., & Storz, P. (2017). Targeting reactive oxygen species in development and progression of pancreatic cancer. Expert Rev Anticancer Ther, 17(1), 19-31. doi:10.1080/14737140.2017.1261017
Feng, Q., Bian, X., Liu, X., Wang, Y., Zhou, H., Ma, X., . . . Zheng, Z. (2020). Intracellular expression of arginine deiminase activates the mitochondrial apoptosis pathway through inhibiting cytosolic ferritin and inducing chromotin autophagy.
Filomeni, G., De Zio, D., & Cecconi, F. (2015a). Oxidative stress and autophagy: the clash between damage and metabolic needs. Cell Death Differ, 22(3), 377-388. doi:10.1038/cdd.2014.150
Filomeni, G., De Zio, D., & Cecconi, F. (2015b). Oxidative stress and autophagy: the clash between damage and metabolic needs. Cell Death & Differentiation, 22(3), 377-388. doi:10.1038/cdd.2014.150
Fridovich, I. (1997). Superoxide anion radical (O2-.), superoxide dismutases, and related matters. J Biol Chem, 272(30), 18515-18517. doi:10.1074/jbc.272.30.18515
Fukui, M., Kang, K. S., Okada, K., & Zhu, B. T. (2013). EPA, an omega‐3 fatty acid, induces apoptosis in human pancreatic cancer cells: role of ROS accumulation, caspase‐8 activation, and autophagy induction. Journal of cellular biochemistry, 114(1), 192-203.
Hakem, R. (2008). DNA-damage repair; the good, the bad, and the ugly. The EMBO journal, 27(4), 589-605. doi:10.1038/emboj.2008.15
Hamacher-Brady, A., & Brady, N. R. (2016). Mitophagy programs: mechanisms and physiological implications of mitochondrial targeting by autophagy. Cell Mol Life Sci, 73(4), 775-795. doi:10.1007/s00018-015-2087-8
Harris, I. S., & DeNicola, G. M. (2020). The complex interplay between antioxidants and ROS in cancer. Trends in Cell Biology, 30(6), 440-451.
He, F., Ru, X., & Wen, T. (2020). NRF2, a transcription factor for stress response and beyond. International Journal of Molecular Sciences, 21(13), 4777.
Hewitt, G., Carroll, B., Sarallah, R., Correia-Melo, C., Ogrodnik, M., Nelson, G., . . . Korolchuk, V. I. (2016). SQSTM1/p62 mediates crosstalk between autophagy and the UPS in DNA repair. Autophagy, 12(10), 1917-1930. doi:10.1080/15548627.2016.1210368
Hewitt, G., & Korolchuk, V. I. (2017). Repair, Reuse, Recycle: The Expanding Role of Autophagy in Genome Maintenance. Trends in Cell Biology, 27(5), 340-351. doi:https://doi.org/10.1016/j.tcb.2016.11.011
Hoeijmakers, J. H. J. (2009). DNA Damage, Aging, and Cancer. New England Journal of Medicine, 361(15), 1475-1485. doi:10.1056/NEJMra0804615
Huang, Y., Guerrero-Preston, R., & Ratovitski, E. A. (2012). Phospho-ΔNp63α-dependent regulation of autophagic signaling through transcription and micro-RNA modulation. Cell cycle, 11(6), 1247-1259.
Huang, Y., Park, Y. C., Rich, R. L., Segal, D., Myszka, D. G., & Wu, H. (2001). Structural Basis of Caspase Inhibition by XIAP: Differential Roles of the Linker versus the BIR Domain. Cell, 104(5), 781-790. doi:10.1016/S0092-8674(01)00273-2
Jaiswal, P. K., Goel, A., & Mittal, R. (2015). Survivin: A molecular biomarker in cancer. The Indian journal of medical research, 141(4), 389.
Jaiswal, P. K., Goel, A., & Mittal, R. D. (2015). Survivin: A molecular biomarker in cancer. Indian J Med Res, 141(4), 389-397. doi:10.4103/0971-5916.159250
Jeppesen, D. K., Bohr, V. A., & Stevnsner, T. (2011). DNA repair deficiency in neurodegeneration. Prog Neurobiol, 94(2), 166-200. doi:10.1016/j.pneurobio.2011.04.013
Jeyaprakash, A. A., Klein, U. R., Lindner, D., Ebert, J., Nigg, E. A., & Conti, E. (2007). Structure of a Survivin–Borealin–INCENP core complex reveals how chromosomal passengers travel together. Cell, 131(2), 271-285.
Jiang, Y., & Chu, W. (2018). Potential Roles of the Retinoblastoma Protein in Regulating Genome Editing. Frontiers in Cell and Developmental Biology, 6. doi:10.3389/fcell.2018.00081
Johnson, J. A., Johnson, D. A., Kraft, A. D., Calkins, M. J., Jakel, R. J., Vargas, M. R., & Chen, P. C. (2008). The Nrf2-ARE pathway: an indicator and modulator of oxidative stress in neurodegeneration. Ann N Y Acad Sci, 1147, 61-69. doi:10.1196/annals.1427.036
Kalvari, I., Tsompanis, S., Mulakkal, N. C., Osgood, R., Johansen, T., Nezis, I. P., & Promponas, V. J. (2014). iLIR: A web resource for prediction of Atg8-family interacting proteins. Autophagy, 10(5), 913-925.
Karantza-Wadsworth, V., Patel, S., Kravchuk, O., Chen, G., Mathew, R., Jin, S., & White, E. (2007). Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis. Genes & development, 21(13), 1621-1635.
Katsuragi, Y., Ichimura, Y., & Komatsu, M. (2016). Regulation of the Keap1–Nrf2 pathway by p62/SQSTM1. Current Opinion in Toxicology, 1, 54-61. doi:https://doi.org/10.1016/j.cotox.2016.09.005
Kim, G. D., Choi, Y. H., Dimtchev, A., Jeong, S. J., Dritschilo, A., & Jung, M. (1999). Sensing of ionizing radiation-induced DNA damage by ATM through interaction with histone deacetylase. J Biol Chem, 274(44), 31127-31130. doi:10.1074/jbc.274.44.31127
Komatsu, M., Waguri, S., Ueno, T., Iwata, J., Murata, S., Tanida, I., . . . Chiba, T. (2005). Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J Cell Biol, 169(3), 425-434. doi:10.1083/jcb.200412022
Kung, H.-J., Changou, C. A., Li, C.-F., & Ann, D. K. (2015). Chromatophagy: autophagy goes nuclear and captures broken chromatin during arginine-starvation. Autophagy, 11(2), 419-421.
Lamark, T., Kirkin, V., Dikic, I., & Johansen, T. (2009). NBR1 and p62 as cargo receptors for selective autophagy of ubiquitinated targets. Cell cycle (Georgetown, Tex.), 8, 1986-1990. doi:10.4161/cc.8.13.8892
Levine, B., & Kroemer, G. (2008). Autophagy in the Pathogenesis of Disease. Cell, 132(1), 27-42. doi:https://doi.org/10.1016/j.cell.2007.12.018
Li, F., Ambrosini, G., Chu, E. Y., Plescia, J., Tognin, S., Marchisio, P. C., & Altieri, D. C. (1998). Control of apoptosis and mitotic spindle checkpoint by survivin. Nature, 396(6711), 580-584. doi:10.1038/25141
Li, Y., Jiang, X., Zhang, Y., Gao, Z., Liu, Y., Hu, J., . . . Gao, N. (2019). Nuclear accumulation of UBC9 contributes to SUMOylation of lamin A/C and nucleophagy in response to DNA damage. Journal of Experimental & Clinical Cancer Research, 38(1), 67. doi:10.1186/s13046-019-1048-8
Liang, D. H., Choi, D. S., Ensor, J. E., Kaipparettu, B. A., Bass, B. L., & Chang, J. C. (2016). The autophagy inhibitor chloroquine targets cancer stem cells in triple negative breast cancer by inducing mitochondrial damage and impairing DNA break repair. Cancer letters, 376(2), 249-258.
Lilienbaum, A. (2013). Relationship between the proteasomal system and autophagy. Int J Biochem Mol Biol, 4(1), 1-26.
Lin, T. Y., Chan, H. H., Chen, S. H., Sarvagalla, S., Chen, P. S., Coumar, M. S., . . . Cheung, C. H. A. (2020). BIRC5/Survivin is a novel ATG12-ATG5 conjugate interactor and an autophagy-induced DNA damage suppressor in human cancer and mouse embryonic fibroblast cells. Autophagy, 16(7), 1296-1313. doi:10.1080/15548627.2019.1671643
Liou, G. Y., & Storz, P. (2010). Reactive oxygen species in cancer. Free Radic Res, 44(5), 479-496. doi:10.3109/10715761003667554
Lister, A., Nedjadi, T., Kitteringham, N. R., Campbell, F., Costello, E., Lloyd, B., . . . Neoptolemos, J. P. (2011). Nrf2 is overexpressed in pancreatic cancer: implications for cell proliferation and therapy. Molecular cancer, 10(1), 1-13.
Liu, T., Brouha, B., & Grossman, D. (2004). Rapid induction of mitochondrial events and caspase-independent apoptosis in Survivin-targeted melanoma cells. Oncogene, 23(1), 39-48. doi:10.1038/sj.onc.1206978
Liu, W. J., Ye, L., Huang, W. F., Guo, L. J., Xu, Z. G., Wu, H. L., . . . Liu, H. F. (2016). p62 links the autophagy pathway and the ubiqutin–proteasome system upon ubiquitinated protein degradation. Cellular & Molecular Biology Letters, 21(1), 29. doi:10.1186/s11658-016-0031-z
Moriai, R., Tsuji, N., Moriai, M., Kobayashi, D., & Watanabe, N. (2009). Survivin plays as a resistant factor against tamoxifen-induced apoptosis in human breast cancer cells. Breast cancer research and treatment, 117(2), 261-271.
Myeku, N., & Figueiredo-Pereira, M. E. (2011). Dynamics of the degradation of ubiquitinated proteins by proteasomes and autophagy: association with sequestosome 1/p62. J Biol Chem, 286(25), 22426-22440. doi:10.1074/jbc.M110.149252
Nomura, T., Yamasaki, M., Nomura, Y., & Mimata, H. (2005). Expression of the inhibitors of apoptosis proteins in cisplatin-resistant prostate cancer cells. Oncology reports, 14(4), 993-997.
O'Connor, D. S., Grossman, D., Plescia, J., Li, F., Zhang, H., Villa, A., . . . Altieri, D. C. (2000). Regulation of apoptosis at cell division by p34cdc2 phosphorylation of survivin. Proc Natl Acad Sci U S A, 97(24), 13103-13107. doi:10.1073/pnas.240390697
Parzych, K. R., & Klionsky, D. J. (2014). An overview of autophagy: morphology, mechanism, and regulation. Antioxid Redox Signal, 20(3), 460-473. doi:10.1089/ars.2013.5371
Paull, T. T., Rogakou, E. P., Yamazaki, V., Kirchgessner, C. U., Gellert, M., & Bonner, W. M. (2000). A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage. Current Biology, 10(15), 886-895. doi:https://doi.org/10.1016/S0960-9822(00)00610-2
Piya, S., Kornblau, S. M., Ruvolo, V. R., Mu, H., Ruvolo, P. P., McQueen, T., . . . Borthakur, G. (2016). Atg7 suppression enhances chemotherapeutic agent sensitivity and overcomes stroma-mediated chemoresistance in acute myeloid leukemia. Blood, 128(9), 1260-1269. doi:10.1182/blood-2016-01-692244
Qiu, D. M., Wang, G. L., Chen, L., Xu, Y. Y., He, S., Cao, X. L., . . . E, Q. (2014). The expression of beclin-1, an autophagic gene, in hepatocellular carcinoma associated with clinical pathological and prognostic significance. BMC Cancer, 14, 327. doi:10.1186/1471-2407-14-327
Qu, X., Yu, J., Bhagat, G., Furuya, N., Hibshoosh, H., Troxel, A., . . . Ohsumi, Y. (2003). Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. The Journal of clinical investigation, 112(12), 1809-1820.
Sarkar, S., Ravikumar, B., & Rubinsztein, D. C. (2009). Autophagic clearance of aggregate-prone proteins associated with neurodegeneration. Methods Enzymol, 453, 83-110. doi:10.1016/s0076-6879(08)04005-6
Schumacker, P. T. (2006). Reactive oxygen species in cancer cells: Live by the sword, die by the sword. Cancer Cell, 10(3), 175-176. doi:https://doi.org/10.1016/j.ccr.2006.08.015
Shin, S., Sung, B.-J., Cho, Y.-S., Kim, H.-J., Ha, N.-C., Hwang, J.-I., . . . Oh, B.-H. (2001). An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and-7. Biochemistry, 40(4), 1117-1123.
Shiozaki, E. N., Chai, J., Rigotti, D. J., Riedl, S. J., Li, P., Srinivasula, S. M., . . . Shi, Y. (2003). Mechanism of XIAP-mediated inhibition of caspase-9. Mol Cell, 11(2), 519-527. doi:10.1016/s1097-2765(03)00054-6
Smolewski, P., & Robak, T. (2011). Inhibitors of apoptosis proteins (IAPs) as potential molecular targets for therapy of hematological malignancies. Curr Mol Med, 11(8), 633-649. doi:10.2174/156652411797536723
Song, Z., Yao, X., & Wu, M. (2003). Direct interaction between survivin and Smac/DIABLO is essential for the anti-apoptotic activity of survivin during taxol-induced apoptosis. Journal of Biological Chemistry, 278(25), 23130-23140.
Storz, P. (2005). Reactive oxygen species in tumor progression. Front Biosci, 10(1-3), 1881-1896.
Taguchi, K., Motohashi, H., & Yamamoto, M. (2011). Molecular mechanisms of the Keap1–Nrf2 pathway in stress response and cancer evolution. Genes to Cells, 16(2), 123-140. doi:https://doi.org/10.1111/j.1365-2443.2010.01473.x
Takamura, A., Komatsu, M., Hara, T., Sakamoto, A., Kishi, C., Waguri, S., . . . Mizushima, N. (2011). Autophagy-deficient mice develop multiple liver tumors. Genes Dev, 25(8), 795-800. doi:10.1101/gad.2016211
Tavares, E. M., Wright, W. D., Heyer, W.-D., Le Cam, E., & Dupaigne, P. (2019). In vitro role of Rad54 in Rad51-ssDNA filament-dependent homology search and synaptic complexes formation. Nature Communications, 10(1), 4058. doi:10.1038/s41467-019-12082-z
Tran, J., Master, Z., Joanne, L. Y., Rak, J., Dumont, D. J., & Kerbel, R. S. (2002). A role for survivin in chemoresistance of endothelial cells mediated by VEGF. Proceedings of the National Academy of Sciences, 99(7), 4349-4354.
Vaux, D. L., & Silke, J. (2005). IAPs, RINGs and ubiquitylation. Nature Reviews Molecular Cell Biology, 6(4), 287-297. doi:10.1038/nrm1621
Waligórska-Stachura, J., Jankowska, A., Waśko, R., Liebert, W., Biczysko, M., Czarnywojtek, A., . . . Ruchała, M. (2012). Survivin–prognostic tumor biomarker in human neoplasms–review. Ginekologia polska, 83(7).
Wang, J., & Wu, G. S. (2014). Role of autophagy in cisplatin resistance in ovarian cancer cells. J Biol Chem, 289(24), 17163-17173. doi:10.1074/jbc.M114.558288
Wei, H., Wei, S., Gan, B., Peng, X., Zou, W., & Guan, J. L. (2011). Suppression of autophagy by FIP200 deletion inhibits mammary tumorigenesis. Genes Dev, 25(14), 1510-1527. doi:10.1101/gad.2051011
Weydert, C. J., & Cullen, J. J. (2010). Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue. Nat Protoc, 5(1), 51-66. doi:10.1038/nprot.2009.197
White, K. A. M., Luo, L., Thompson, T. A., Torres, S., Hu, C.-A. A., Thomas, N. E., . . . Group, T. G. S. (2016). Variants in autophagy-related genes and clinical characteristics in melanoma: a population-based study. Cancer Medicine, 5(11), 3336-3345. doi:https://doi.org/10.1002/cam4.929
Wiesmüller, L., Ford, J. M., & Schiestl, R. H. (2002). DNA Damage, Repair, and Diseases. J Biomed Biotechnol, 2(2), 45. doi:10.1155/s1110724302001985
Yang, X., Yu, D.-D., Yan, F., Jing, Y.-Y., Han, Z.-P., Sun, K., . . . Wei, L.-X. (2015). The role of autophagy induced by tumor microenvironment in different cells and stages of cancer. Cell & bioscience, 5(1), 1-11.
Zou, Z., Chang, H., Li, H., & Wang, S. (2017). Induction of reactive oxygen species: an emerging approach for cancer therapy. Apoptosis, 22(11), 1321-1335.