EGFR family members’ regulation of autophagy is at a crossroads of cell survival and death in cancer

Cancers

Volumn 9, Issue 4, 2017, Pages

  Henson, Elizabeth ^a   Chen, Yongqiang ^a   Gibson, Spencer ^a,b  

^a UNIVERSITY OF MANITOBA   (Canada)

^b UNIVERSITY OF MANITOBA   (Canada)

Author keywords

Autophagy; Beclin 1; Epidermal growth factor; Mitochondria; Signaling

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR 3; EPIDERMAL GROWTH FACTOR RECEPTOR 4; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR;

APOPTOSIS; AUTOPHAGY; CANCER CELL DESTRUCTION; CANCER RESISTANCE; CELL DEATH; CELL SURVIVAL; HUMAN; MALIGNANT NEOPLASM; NONHUMAN; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION;

EID: 85016457278     PISSN: None     EISSN: 20726694     Source Type: Journal    
DOI: 10.3390/cancers9040027     Document Type: Review

References (83)

1. Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: the next generation. Cell 2011, 144, 646–674. [CrossRef] [PubMed]
2. Jutten, B.; Rouschop, K.M. EGFR signaling and autophagy dependence for growth, survival, and therapy resistance. Cell Cycle 2014, 13, 42–51. [CrossRef] [PubMed]
3. Wieduwilt, M.J.; Moasser, M.M. The epidermal growth factor receptor family: biology driving targeted therapeutics. Cell Mol. Life Sci. 2008, 65, 1566–1584. [CrossRef] [PubMed]
4. Henson, E.S.; Gibson, S.B. Surviving cell death through epidermal growth factor (EGF) signal transduction pathways: implications for cancer therapy. Cell Signal 2006, 18, 2089–2097. [CrossRef] [PubMed]
5. Hynes, N.E.; Lane, H.A. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat. Rev. Cancer 2005, 5, 341–354. [CrossRef] [PubMed]
6. Yarden, Y.; Sliwkowski, M.X. Untangling the ErbB signalling network. Nat. Rev. Mol. Cell Biol. 2001, 2, 127–137. [CrossRef] [PubMed]
7. Lindsey, S.; Langhans, S.A. Epidermal growth factor signaling in transformed cells. Int. Rev. Cell Mol. Biol. 2015, 314, 1–41. [PubMed]
8. Normanno, N.; Bianco, C.; Strizzi, L.; Mancino, M.; Maiello, M.R.; De Luca, A.; Caponigro, F.; Salomon, D.S. The ErbB receptors and their ligands in cancer: an overview. Curr. Drug Targets 2005, 6, 243–257. [CrossRef] [PubMed]
9. Jonsson, G.; Staaf, J.; Vallon-Christersson, J.; Ringner, M.; Holm, K.; Hegardt, C.; Gunnarsson, H.; Fagerholm, R.; Strand, C.; Agnarsson, B.A.; et al. Genomic subtypes of breast cancer identified by array-comparative genomic hybridization display distinct molecular and clinical characteristics. Breast Cancer Res.: BCR. 2010, 12, R42. [CrossRef] [PubMed]
10. Amann, J.; Kalyankrishna, S.; Massion, P.P.; Ohm, J.E.; Girard, L.; Shigematsu, H.; Peyton, M.; Juroske, D.; Huang, Y.; Stuart, S.J.; et al. Aberrant epidermal growth factor receptor signaling and enhanced sensitivity to EGFR inhibitors in lung cancer. Cancer Res. 2005, 65, 226–235. [PubMed]
11. Pedersen, M.W.; Meltorn, M.; Damstrup, L.; Poulsen, H.S. The type III epidermal growth factor receptor mutation. Biological significance and potential target for anti-cancer therapy. Ann. Oncol. 2001, 12, 745–760. [CrossRef] [PubMed]
12. Cuello, M.; Ettenberg, S.A.; Clark, A.S.; Keane, M.M.; Posner, R.H.; Nau, M.M.; Dennis, P.A.; Lipkowitz, S. Down-regulation of the erbB-2 receptor by trastuzumab (herceptin) enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in breast and ovarian cancer cell lines that overexpress erbB-2. Cancer Res. 2001, 61, 4892–4900. [PubMed]
13. Izumi, Y.; Xu, L.; di Tomaso, E.; Fukumura, D.; Jain, R.K. Tumour biology: herceptin acts as an anti-angiogenic cocktail. Nature 2002, 416, 279–280. [CrossRef] [PubMed]
14. Longva, K.E.; Pedersen, N.M.; Haslekas, C.; Stang, E.; Madshus, I.H. Herceptin-induced inhibition of ErbB2 signaling involves reduced phosphorylation of Akt but not endocytic down-regulation of ErbB2. Int. J. Cancer 2005, 116, 359–367. [CrossRef] [PubMed]
15. Luque-Cabal, M.; Garcia-Teijido, P.; Fernandez-Perez, Y.; Sanchez-Lorenzo, L.; Palacio-Vazquez, I. Mechanisms Behind the Resistance to Trastuzumab in HER2-Amplified Breast Cancer and Strategies to Overcome It. Clin. Med. Insights Oncol. 2016, 10, 21–30. [CrossRef] [PubMed]
16. Ma, J.; Lyu, H.; Huang, J.; Liu, B. Targeting of erbB3 receptor to overcome resistance in cancer treatment. Mol. Cancer 2014, 13, 105. [CrossRef] [PubMed]
17. Matsumoto, K.; Umitsu, M.; De Silva, D.M.; Roy, A.; Bottaro, D.P. HGF-MET in cancer progression and biomarker discovery. Cancer Sci. 2017. [CrossRef] [PubMed]
18. Ito, Y.; Tokudome, N.; Sugihara, T.; Takahashi, S.; Hatake, K. Does lapatinib, a small-molecule tyrosine kinase inhibitor, constitute a breakthrough in the treatment of breast cancer? Breast Cancer 2007, 14, 156–162. [CrossRef] [PubMed]
19. Browne, B.C.; O’Brien, N.; Duffy, M.J.; Crown, J.; O’Donovan, N. HER-2 signaling and inhibition in breast cancer. Curr. Cancer Drug Targets 2009, 9, 419–438. [CrossRef] [PubMed]
20. Moy, B.; Goss, P.E. Lapatinib: current status and future directions in breast cancer. Oncologist 2006, 11, 1047–1057. [CrossRef] [PubMed]
21. Ruprecht, B.; Zaal, E.A.; Zecha, J.; Wu, W.; Berkers, C.R.; Kuster, B.; Lemeer, S. Lapatinib resistance in breast cancer cells is accompanied by phosphorylation-mediated reprogramming of glycolysis. Cancer Res. 2017. [CrossRef] [PubMed]
22. Kancha, R.K.; von Bubnoff, N.; Bartosch, N.; Peschel, C.; Engh, R.A.; Duyster, J. Differential sensitivity of ERBB2 kinase domain mutations towards lapatinib. PLoS ONE 2011, 6, e26760. [CrossRef] [PubMed]
23. Franklin, M.C.; Carey, K.D.; Vajdos, F.F.; Leahy, D.J.; De Vos, A.M.; Sliwkowski, M.X. Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell 2004, 5, 317–328. [CrossRef]
24. Nahta, R.; Hung, M.C.; Esteva, F.J. The HER-2-targeting antibodies trastuzumab and pertuzumab synergistically inhibit the survival of breast cancer cells. Cancer Res. 2004, 64, 2343–2346. [CrossRef] [PubMed]
25. Ma, L.; Zhang, G.; Miao, X.B.; Deng, X.B.; Wu, Y.; Liu, Y.; Jin, Z.R.; Li, X.Q.; Liu, Q.Z.; Sun, D.X.; et al. Cancer stem-like cell properties are regulated by EGFR/AKT/beta-catenin signaling and preferentially inhibited by gefitinib in nasopharyngeal carcinoma. FEBS J. 2013, 280, 2027–2041. [CrossRef] [PubMed]
26. Arora, A.; Scholar, E.M. Role of Tyrosine Kinase Inhibitors in Cancer Therapy. J. Pharmacol. Exp. Ther. 2005, 315, 971–979. [CrossRef] [PubMed]
27. Yun, C.H.; Mengwasser, K.E.; Toms, A.V.; Woo, M.S.; Greulich, H.; Wong, K.K.; Meyerson, M.; Eck, M.J. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. PNAS 2008, 105, 2070–2075. [CrossRef] [PubMed]
28. Dassonville, O.; Bozec, A.; Fischel, J.L.; Milano, G. EGFR targeting therapies: monoclonal antibodies versus tyrosine kinase inhibitors. Similarities and differences. Crit. Rev. Oncol. Hematol. 2007, 62, 53–61. [CrossRef] [PubMed]
29. Normanno, N.; De Luca, A.; Maiello, M.R.; Campiglio, M.; Napolitano, M.; Mancino, M.; Carotenuto, A.; Viglietto, G.; Menard, S. The MEK/MAPK pathway is involved in the resistance of breast cancer cells to the EGFR tyrosine kinase inhibitor gefitinib. J. Cell. Physiol. 2006, 207, 420–427. [CrossRef] [PubMed]
30. Widmann, C.; Gibson, S.; Jarpe, M.B.; Johnson, G.L. Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol. Rev. 1999, 79, 143–180. [PubMed]
31. Fang, J.Y.; Richardson, B.C. The MAPK signalling pathways and colorectal cancer. Lancet Oncol. 2005, 6, 322–327. [CrossRef]
32. Booy, E.P.; Henson, E.S.; Gibson, S.B. Epidermal growth factor regulates Mcl-1 expression through the MAPK-Elk-1 signalling pathway contributing to cell survival in breast cancer. Oncogene 2011, 30, 2367–2378. [CrossRef] [PubMed]
33. Kawasaki, Y.; Sakimura, A.; Park, C.M.; Tomaru, R.; Tanaka, T.; Ozawa, T.; Zhou, Y.; Narita, K.; Kishi, H.; Muraguchi, A.; et al. Feedback control of ErbB2 via ERK-mediated phosphorylation of a conserved threonine in the juxtamembrane domain. Sci. Rep. 2016, 6, 31502. [CrossRef] [PubMed]
34. Lux, M.P.; Fasching, P.A.; Schrauder, M.G.; Hein, A.; Jud, S.M.; Rauh, C.; Beckmann, M.W. The PI3K Pathway: Background and Treatment Approaches. Breast Care 2016, 11, 398–404. [CrossRef] [PubMed]
35. Nandini, D.; Pradip, D.; Brian, L.J. PI3K-AKT-mTOR inhibitors in breast cancers: From tumor cell signaling to clinical trials. Pharmacol. Ther. 2017. [CrossRef]
36. Quesnelle, K.M.; Boehm, A.L.; Grandis, J.R. STAT-mediated EGFR signaling in cancer. J. Cell. Biochem. 2007, 102, 311–319. [CrossRef] [PubMed]
37. Barbieri, E.; Di Fiore, P.P.; Sigismund, S. Endocytic control of signaling at the plasma membrane. Curr. Opin. Cell Biol. 2016, 39, 21–27. [CrossRef] [PubMed]
38. Lo, H.W.; Hsu, S.C.; Ali-Seyed, M.; Gunduz, M.; Xia, W.; Wei, Y.; Bartholomeusz, G.; Shih, J.Y.; Hung, M.C. Nuclear interaction of EGFR and STAT3 in the activation of the iNOS/NO pathway. Cancer Cell 2005, 7, 575–589. [CrossRef] [PubMed]
39. Lin, S.Y.; Makino, K.; Xia, W.; Matin, A.; Wen, Y.; Kwong, K.Y.; Bourguignon, L.; Hung, M.C. Nuclear localization of EGF receptor and its potential new role as a transcription factor. Nat. Cell Biol. 2001, 3, 802–808. [CrossRef] [PubMed]
40. Klionsky, D.J.; Abdelmohsen, K.; Abe, A.; Abedin, M.J.; Abeliovich, H.; Acevedo Arozena, A.; Adachi, H.; Adams, C.M.; Adams, P.D.; Adeli, K.; et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 2016, 12, 1–222. [CrossRef] [PubMed]
41. Mizushima, N.; Levine, B.; Cuervo, A.M.; Klionsky, D.J. Autophagy fights disease through cellular self-digestion. Nature 2008, 451, 1069–1075. [CrossRef] [PubMed]
42. Azad, M.B.; Chen, Y.; Gibson, S.B. Regulation of autophagy by reactive oxygen species (ROS): Implications for cancer progression and treatment. Antioxid. Redox Signal. 2009, 11, 777–790. [CrossRef] [PubMed]
43. + -ATPase-regulated form of cell death triggered by autophagy-inducing peptides, starvation, and hypoxia-ischemia. Proc. Natl. Acad. Sci. USA 2013, 110, 20364–20371. [CrossRef] [PubMed]
44. Chen, N.; Debnath, J. Autophagy and tumorigenesis. FEBS Lett. 2010, 584, 1427–1435. [CrossRef] [PubMed]
45. Liang, X.H.; Jackson, S.; Seaman, M.; Brown, K.; Kempkes, B.; Hibshoosh, H.; Levine, B. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 1999, 402, 672–676. [PubMed]
46. Yue, Z.; Jin, S.; Yang, C.; Levine, A.J.; Heintz, N. Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc. Natl. Acad. Sci. USA 2003, 100, 15077–15082. [CrossRef] [PubMed]
47. Qu, X.; Yu, J.; Bhagat, G.; Furuya, N.; Hibshoosh, H.; Troxel, A.; Rosen, J.; Eskelinen, E.L.; Mizushima, N.; Ohsumi, Y.; et al. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J. Clin. Invest. 2003, 112, 1809–1820. [CrossRef] [PubMed]
48. Marino, G.; Salvador-Montoliu, N.; Fueyo, A.; Knecht, E.; Mizushima, N.; Lopez-Otin, C. Tissue-specific autophagy alterations and increased tumorigenesis in mice deficient in Atg4C/autophagin-3. J. Biol. Chem. 2007, 282, 18573–18583. [CrossRef] [PubMed]
49. Jung, C.H.; Jun, C.B.; Ro, S.H.; Kim, Y.M.; Otto, N.M.; Cao, J.; Kundu, M.; Kim, D.H. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol. Biol. Cell 2009, 20, 1992–2003. [CrossRef] [PubMed]
50. Chen, Y.; Henson, E.S.; Xiao, W.; Huang, D.; McMillan-Ward, E.M.; Israels, S.J.; Gibson, S.B. Tyrosine kinase receptor EGFR regulates the switch in cancer cells between cell survival and cell death induced by autophagy in hypoxia. Autophagy 2016, 12, 1029–1046. [CrossRef] [PubMed]
51. Viry, E.; Noman, M.Z.; Arakelian, T.; Lequeux, A.; Chouaib, S.; Berchem, G.; Moussay, E.; Paggetti, J.; Janji, B. Hijacker of the Antitumor Immune Response: Autophagy Is Showing Its Worst Facet. Front Oncol. 2016, 6, 246. [CrossRef] [PubMed]
52. Janji, B.; Viry, E.; Moussay, E.; Paggetti, J.; Arakelian, T.; Mgrditchian, T.; Messai, Y.; Noman, M.Z.; Van Moer, K.; Hasmim, M.; et al. The multifaceted role of autophagy in tumor evasion from immune surveillance. Oncotarget 2016, 7, 17591–17607. [CrossRef] [PubMed]
53. Dragowska, W.H.; Weppler, S.A.; Wang, J.C.; Wong, L.Y.; Kapanen, A.I.; Rawji, J.S.; Warburton, C.; Qadir, M.A.; Donohue, E.; Roberge, M.; et al. Induction of autophagy is an early response to gefitinib and a potential therapeutic target in breast cancer. PLoS ONE 2013, 8, e76503.
54. Wei, Y.; Zou, Z.; Becker, N.; Anderson, M.; Sumpter, R.; Xiao, G.; Kinch, L.; Koduru, P.; Christudass, C.S.; Veltri, R.W.; et al. EGFR-mediated Beclin 1 phosphorylation in autophagy suppression, tumor progression, and tumor chemoresistance. Cell 2013, 154, 1269–1284. [CrossRef] [PubMed]
55. Chen, Z.; Gao, S.; Wang, D.; Song, D.; Feng, Y. Colorectal cancer cells are resistant to anti-EGFR monoclonal antibody through adapted autophagy. Am. J. Transl. Res. 2016, 8, 1190–1196. [PubMed]
56. Pattingre, S.; Tassa, A.; Qu, X.; Garuti, R.; Liang, X.H.; Mizushima, N.; Packer, M.; Schneider, M.D.; Levine, B. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 2005, 122, 927–939. [CrossRef] [PubMed]
57. Xu, B.; Gogol, M.; Gaudenz, K.; Gerton, J.L. Improved transcription and translation with L-leucine stimulation of mTORC1 in Roberts syndrome. BMC Genomics 2016, 17, 25. [CrossRef] [PubMed]
58. Tan, X.; Thapa, N.; Sun, Y.; Anderson, R.A. A kinase-independent role for EGF receptor in autophagy initiation. Cell 2015, 160, 145–160. [CrossRef] [PubMed]
59. Sobhakumari, A.; Schickling, B.M.; Love-Homan, L.; Raeburn, A.; Fletcher, E.V.; Case, A.J.; Domann, F.E.; Miller, F.J.; Simons, A.L. NOX4 mediates cytoprotective autophagy induced by the EGFR inhibitor erlotinib in head and neck cancer cells. Toxicol. Appl. Pharmacol. 2013, 272, 736–745. [CrossRef] [PubMed]
60. Li, X.; Fan, Z. The epidermal growth factor receptor antibody cetuximab induces autophagy in cancer cells by downregulating HIF-1alpha and Bcl-2 and activating the beclin 1/hVps34 complex. Cancer Res. 2010, 70, 5942–5952. [CrossRef] [PubMed]
61. Yang, Z.; Liu, Y.; Wei, X.; Zhou, X.; Gong, C.; Zhang, T.; Jin, P.; Xu, S.; Ma, D.; Gao, Q. Co-targeting EGFR and Autophagy Impairs Ovarian Cancer Cell Survival during Detachment from the ECM. Curr. Cancer Drug Targets 2015, 15, 215–226. [CrossRef] [PubMed]
62. Tang, M.C.; Wu, M.Y.; Hwang, M.H.; Chang, Y.T.; Huang, H.J.; Lin, A.M.; Yang, J.C. Chloroquine enhances gefitinib cytotoxicity in gefitinib-resistant nonsmall cell lung cancer cells. PLoS ONE 2015, 10, e0119135. [CrossRef] [PubMed]
63. Wang, Z.; Du, T.; Dong, X.; Li, Z.; Wu, G.; Zhang, R. Autophagy inhibition facilitates erlotinib cytotoxicity in lung cancer cells through modulation of endoplasmic reticulum stress. Int. J. Oncol. 2016, 48, 2558–2566. [CrossRef] [PubMed]
64. Fung, C.; Chen, X.; Grandis, J.R.; Duvvuri, U. EGFR tyrosine kinase inhibition induces autophagy in cancer cells. Cancer Biol. Ther. 2012, 13, 1417–1424. [CrossRef] [PubMed]
65. So, K.S.; Kim, C.H.; Rho, J.K.; Kim, S.Y.; Choi, Y.J.; Song, J.S.; Kim, W.S.; Choi, C.M.; Chun, Y.J.; Lee, J.C. Autophagosome-mediated EGFR down-regulation induced by the CK2 inhibitor enhances the efficacy of EGFR-TKI on EGFR-mutant lung cancer cells with resistance by T790M. PLoS ONE 2014, 9, e114000. [CrossRef] [PubMed]
66. Mu, L.; Wang, T.; Chen, Y.; Tang, X.; Yuan, Y.; Zhao, Y. beta-Elemene enhances the efficacy of gefitinib on glioblastoma multiforme cells through the inhibition of the EGFR signaling pathway. Int. J. Oncol. 2016, 49, 1427–1436. [PubMed]
67. Jutten, B.; Keulers, T.G.; Schaaf, M.B.; Savelkouls, K.; Theys, J.; Span, P.N.; Vooijs, M.A.; Bussink, J.; Rouschop, K.M. EGFR overexpressing cells and tumors are dependent on autophagy for growth and survival. Radiother. Oncol. 2013, 108, 479–483. [CrossRef] [PubMed]
68. Weihua, Z.; Tsan, R.; Huang, W.C.; Wu, Q.; Chiu, C.H.; Fidler, I.J.; Hung, M.C. Survival of cancer cells is maintained by EGFR independent of its kinase activity. Cancer Cell 2008, 13, 385–393. [CrossRef] [PubMed]
69. Yue, X.; Song, W.; Zhang, W.; Chen, L.; Xi, Z.; Xin, Z.; Jiang, X. Mitochondrially localized EGFR is subjected to autophagic regulation and implicated in cell survival. Autophagy 2008, 4, 641–649. [CrossRef] [PubMed]
70. Xu, S.W.; Law, B.Y.; Mok, S.W.; Leung, E.L.; Fan, X.X.; Coghi, P.S.; Zeng, W.; Leung, C.H.; Ma, D.L.; Liu, L.; et al. Autophagic degradation of epidermal growth factor receptor in gefitinib-resistant lung cancer by celastrol. Int. J. Oncol. 2016, 49, 1576–1588. [CrossRef] [PubMed]
71. Han, J.; Hou, W.; Lu, C.; Goldstein, L.A.; Stolz, D.B.; Watkins, S.C.; Rabinowich, H. Interaction between Her2 and Beclin-1 proteins underlies a new mechanism of reciprocal regulation. J. Biol. Chem. 2013, 288, 20315–20325. [CrossRef] [PubMed]
72. Choi, J.; Jung, W.; Koo, J.S. Expression of autophagy-related markers beclin-1, light chain 3A, light chain 3B and p62 according to the molecular subtype of breast cancer. Histopathol. 2013, 62, 275–286. [CrossRef] [PubMed]
73. Cufi, S.; Vazquez-Martin, A.; Oliveras-Ferraros, C.; Corominas-Faja, B.; Cuyas, E.; Lopez-Bonet, E.; Martin-Castillo, B.; Joven, J.; Menendez, J.A. The anti-malarial chloroquine overcomes primary resistance and restores sensitivity to trastuzumab in HER2-positive breast cancer. Sci. Rep. 2013, 3, 2469. [CrossRef] [PubMed]
74. Bortnik, S.; Choutka, C.; Horlings, H.M.; Leung, S.; Baker, J.H.; Lebovitz, C.; Dragowska, W.H.; Go, N.E.; Bally, M.B.; Minchinton, A.I.; et al. Identification of breast cancer cell subtypes sensitive to ATG4B inhibition. Oncotarget 2016, 7, 66970–66988. [CrossRef] [PubMed]
75. Rodriguez, C.E.; Reidel, S.I.; Bal de Kier Joffe, E.D.; Jasnis, M.A.; Fiszman, G.L. Autophagy Protects from Trastuzumab-Induced Cytotoxicity in HER2 Overexpressing Breast Tumor Spheroids. PLoS ONE 2015, 10, e0137920. [CrossRef] [PubMed]
76. Zhu, X.; Wu, L.; Qiao, H.; Han, T.; Chen, S.; Liu, X.; Jiang, R.; Wei, Y.; Feng, D.; Zhang, Y.; et al. Autophagy stimulates apoptosis in HER2-overexpressing breast cancers treated by lapatinib. J. Cell. Biochem. 2013, 114, 2643–2653. [CrossRef] [PubMed]
77. Chen, Y.J.; Chi, C.W.; Su, W.C.; Huang, H.L. Lapatinib induces autophagic cell death and inhibits growth of human hepatocellular carcinoma. Oncotarget 2014, 5, 4845–4854. [CrossRef] [PubMed]
78. Chen, Y.J.; Fang, L.W.; Su, W.C.; Hsu, W.Y.; Yang, K.C.; Huang, H.L. Lapatinib induces autophagic cell death and differentiation in acute myeloblastic leukemia. Onco. Targets Ther. 2016, 9, 4453–4464. [PubMed]
79. Bisaro, B.; Sciortino, M.; Colombo, S.; Leal, M.P.C.; Costamagna, A.; Castellano, I.; Montemurro, F.; Rossi, V.; Valabrega, G.; Turco, E.; et al. p130Cas scaffold protein regulates ErbB2 stability by altering breast cancer cell sensitivity to autophagy. Oncotarget 2016, 7, 4442–4453. [PubMed]
80. Nunes, J.; Zhang, H.; Angelopoulos, N.; Chhetri, J.; Osipo, C.; Grothey, A.; Stebbing, J.; Giamas, G. ATG9A loss confers resistance to trastuzumab via c-Cbl mediated Her2 degradation. Oncotarget 2016, 7, 27599–27612. [PubMed]
81. Chiacchiera, F.; Grossi, V.; Cappellari, M.; Peserico, A.; Simonatto, M.; Germani, A.; Russo, S.; Moyer, M.P.; Resta, N.; Murzilli, S.; et al. Blocking p38/ERK crosstalk affects colorectal cancer growth by inducing apoptosis in vitro and in preclinical mouse models. Cancer Lett. 2012, 324, 98–108. [CrossRef] [PubMed]
82. Tsai, C.W.; Lai, F.J.; Sheu, H.M.; Lin, Y.S.; Chang, T.H.; Jan, M.S.; Chen, S.M.; Hsu, P.C.; Huang, T.T.; Huang, T.C.; et al. WWOX suppresses autophagy for inducing apoptosis in methotrexate-treated human squamous cell carcinoma. Cell Death Dis. 2013, 4, e792. [CrossRef] [PubMed]
83. Aqeilan, R.I.; Donati, V.; Gaudio, E.; Nicoloso, M.S.; Sundvall, M.; Korhonen, A.; Lundin, J.; Isola, J.; Sudol, M.; Joensuu, H.; et al. Association of Wwox with ErbB4 in breast cancer. Cancer Res. 2007, 67, 9330–9336. [CrossRef] [PubMed]