Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ASCO Annual Meeting 2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

2024 ASCO Annual Meeting

Keep up to date with all the top stories and latest evidence with our hub page, including official congress videos and expert takeaways.
ADVANCED SEARCH
Log in
Top
Molecular Cancer
Published in: Molecular Cancer 1/2019

Open Access 01-12-2019 | Metastasis | Review

Crosstalk between autophagy and epithelial-mesenchymal transition and its application in cancer therapy

Authors: Hong-Tao Chen, Hao Liu, Min-Jie Mao, Yuan Tan, Xiang-Qiong Mo, Xiao-Jun Meng, Meng-Ting Cao, Chu-Yu Zhong, Yan Liu, Hong Shan, Guan-Min Jiang

Published in: Molecular Cancer | Issue 1/2019

Login to get access

Abstract

Autophagy is a highly conserved catabolic process that mediates degradation of pernicious or dysfunctional cellular components, such as invasive pathogens, senescent proteins, and organelles. It can promote or suppress tumor development, so it is a “double-edged sword” in tumors that depends on the cell and tissue types and the stages of tumor. The epithelial-mesenchymal transition (EMT) is a complex biological trans-differentiation process that allows epithelial cells to transiently obtain mesenchymal features, including motility and metastatic potential. EMT is considered as an important contributor to the invasion and metastasis of cancers. Thus, clarifying the crosstalk between autophagy and EMT will provide novel targets for cancer therapy. It was reported that EMT-related signal pathways have an impact on autophagy; conversely, autophagy activation can suppress or strengthen EMT by regulating various signaling pathways. On one hand, autophagy activation provides energy and basic nutrients for EMT during metastatic spreading, which assists cells to survive in stressful environmental and intracellular conditions. On the other hand, autophagy, acting as a cancer-suppressive function, is inclined to hinder metastasis by selectively down-regulating critical transcription factors of EMT in the early phases. Therefore, the inhibition of EMT by autophagy inhibitors or activators might be a novel strategy that provides thought and enlightenment for the treatment of cancer. In this article, we discuss in detail the role of autophagy and EMT in the development of cancers, the regulatory mechanisms between autophagy and EMT, the effects of autophagy inhibition or activation on EMT, and the potential applications in anticancer therapy.
Literature
1.
2.
Levy JMM, Towers CG, Thorburn A. Targeting autophagy in cancer. Nat Rev Cancer. 2017;17(9):528–42.CrossRefPubMed
3.
4.
Krebs AM, Mitschke J, Lasierra Losada M, et al. The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer. Nat Cell Biol. 2017;19(5):518–29.CrossRefPubMed
5.
Nieto MA. Epithelial plasticity: a common theme in embryonic and cancer cells. Science. 2013;342(6159):1234850.PubMedCrossRef
6.
Singla M, Bhattacharyya S. Autophagy as a potential therapeutic target during epithelial to mesenchymal transition in renal cell carcinoma: An in vitro study. Biomed Pharmacother. 2017;94:332–40.PubMedCrossRef
7.
Catalano M, D'Alessandro G, Lepore F, et al. Autophagy induction impairs migration and invasion by reversing EMT in glioblastoma cells. Mol Oncol. 2015;9(8):1612–25.PubMedPubMedCentralCrossRef
8.
9.
10.
11.
Cheong H, Lu C, Lindsten T, et al. Therapeutic targets in cancer cell metabolism and autophagy. Nat Biotechnol. 2012;30(7):671–8.CrossRefPubMed
12.
DeNardo DG, Barreto JB, Andreu P, et al. CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell. 2009;16(2):91–102.PubMedPubMedCentralCrossRef
13.
Tanaka S, Hosokawa M, Yonezawa T, et al. Induction of epithelial-mesenchymal transition and down-regulation of miR-200c and miR-141 in oxaliplatin-resistant colorectal cancer cells. Biol Pharm Bull. 2015;38(3):435–40.PubMedCrossRef
14.
Xu W, Liu H, Liu ZG, et al. Histone deacetylase inhibitors upregulate snail via Smad2/3 phosphorylation and stabilization of snail to promote metastasis of hepatoma cells. Cancer Lett. 2018;420(2018):1–13.PubMedCrossRef
15.
Saitoh M. Epithelial-mesenchymal transition is regulated at post-transcriptional levels by transforming growth factor-beta signaling during tumor progression. Cancer Sci. 2015;106(5):481–8.PubMedPubMedCentralCrossRef
16.
Matos ML, Lapyckyj L, Rosso M, et al. Identification of a novel human E-cadherin splice variant and assessment of its effects upon EMT-related events. J Cell Physiol. 2017;232(6):1368–86.PubMedCrossRef
17.
18.
19.
Qian Y, Yao W, Yang T, et al. aPKC-iota/P-Sp1/snail signaling induces epithelial-mesenchymal transition and immunosuppression in cholangiocarcinoma. Hepatology. 2017;66(4):1165–82.PubMedCrossRef
20.
Thomson S, Petti F, Sujka-Kwok I, et al. A systems view of epithelial-mesenchymal transition signaling states. Clin Exp Metastasis. 2011;28(2):137–55.PubMedCrossRef
21.
Switon K, Kotulska K, Janusz-Kaminska A, et al. Molecular neurobiology of mTOR. Neuroscience. 2017;341:112–53.PubMedCrossRef
22.
Xue JF, Shi ZM, Zou J, et al. Inhibition of PI3K/AKT/mTOR signaling pathway promotes autophagy of articular chondrocytes and attenuates inflammatory response in rats with osteoarthritis. Biomed Pharmacother. 2017;89:1252–61.PubMedCrossRef
23.
Asati V, Mahapatra DK, Bharti SK. PI3K/Akt/mTOR and Ras/Raf/MEK/ERK signaling pathways inhibitors as anticancer agents: structural and pharmacological perspectives. Eur J Med Chem. 2016;109:314–41.PubMedCrossRef
24.
Mauro L, Naimo GD, Gelsomino L, et al. Uncoupling effects of estrogen receptor alpha on LKB1/AMPK interaction upon adiponectin exposure in breast cancer. FASEB J. 2018;32(8):4343–55.PubMedCrossRef
25.
Renard J, Loureiro M, Rosen LG, et al. Cannabidiol counteracts amphetamine-induced neuronal and behavioral sensitization of the mesolimbic dopamine pathway through a novel mTOR/p70S6 kinase signaling pathway. J Neurosci. 2016;36(18):5160–9.PubMedPubMedCentralCrossRef
26.
So L, Lee J, Palafox M, et al. The 4E-BP-eIF4E axis promotes rapamycin-sensitive growth and proliferation in lymphocytes. Sci Signal. 2016;9(430):ra57.PubMedPubMedCentralCrossRef
27.
Zong H, Yin B, Zhou H, et al. Inhibition of mTOR pathway attenuates migration and invasion of gallbladder cancer via EMT inhibition. Mol Biol Rep. 2014;41(7):4507–12.PubMedCrossRef
28.
Han B, Cui H, Kang L, et al. Metformin inhibits thyroid cancer cell growth, migration, and EMT through the mTOR pathway. Tumour Biol. 2015;36(8):6295–304.PubMedCrossRef
29.
Guo SJ, Liang XX, Guo M, et al. Migration inhibition of water stress proteins from Nostoc commune Vauch via activation of autophagy in DLD-1 cells. Int J Biol Macromol. 2018;119:669–76.PubMedCrossRef
30.
31.
Li L, Pan XY, Shu J, et al. Ribonuclease inhibitor up-regulation inhibits the growth and induces apoptosis in murine melanoma cells through repression of angiogenin and ILK/PI3K/AKT signaling pathway. Biochimie. 2014;103:89–100.PubMedCrossRef
32.
Xu W, Yang Z, Lu N. A new role for the PI3K/Akt signaling pathway in the epithelial-mesenchymal transition. Cell Adhes Migr. 2015;9(4):317–24.CrossRef
33.
Wendt MK, Smith JA, Schiemann WP. Transforming growth factor-beta-induced epithelial-mesenchymal transition facilitates epidermal growth factor-dependent breast cancer progression. Oncogene. 2010;29(49):6485–98.PubMedPubMedCentralCrossRef
34.
Baek SH, Ko JH, Lee JH, et al. Ginkgolic acid inhibits invasion and migration and TGF-beta-induced EMT of lung Cancer cells through PI3K/Akt/mTOR inactivation. J Cell Physiol. 2017;232(2):346–54.PubMedCrossRef
35.
Maier HJ, Schmidt-Strassburger U, Huber MA, et al. NF-kappaB promotes epithelial-mesenchymal transition, migration and invasion of pancreatic carcinoma cells. Cancer Lett. 2010;295(2):214–28.PubMedCrossRef
36.
Peart T, Ramos Valdes Y, Correa RJ, et al. Intact LKB1 activity is required for survival of dormant ovarian cancer spheroids. Oncotarget. 2015;6(26):22424–38.PubMedPubMedCentralCrossRef
37.
Inoki K, Kim J, Guan KL. AMPK and mTOR in cellular energy homeostasis and drug targets. Annu Rev Pharmacol Toxicol. 2012;52:381–400.PubMedCrossRef
38.
Wang P, Jiang L, Zhou N, et al. Resveratrol ameliorates autophagic flux to promote functional recovery in rats after spinal cord injury. Oncotarget. 2018;9(9):8427–40.PubMedPubMedCentral
39.
Sun A, Li C, Chen R, et al. GSK-3beta controls autophagy by modulating LKB1-AMPK pathway in prostate cancer cells. Prostate. 2016;76(2):172–83.PubMedCrossRef
40.
Chang HW, Lee YS, Nam HY, et al. Knockdown of beta-catenin controls both apoptotic and autophagic cell death through LKB1/AMPK signaling in head and neck squamous cell carcinoma cell lines. Cell Signal. 2013;25(4):839–47.PubMedCrossRef
41.
Kan JY, Yen MC, Wang JY, et al. Nesfatin-1/Nucleobindin-2 enhances cell migration, invasion, and epithelial-mesenchymal transition via LKB1/AMPK/TORC1/ZEB1 pathways in colon cancer. Oncotarget. 2016;7(21):31336–49.PubMedPubMedCentralCrossRef
42.
Lin H, Li N, He H, et al. AMPK inhibits the stimulatory effects of TGF-beta on Smad2/3 activity, cell migration, and epithelial-to-mesenchymal transition. Mol Pharmacol. 2015;88(6):1062–71.PubMedPubMedCentralCrossRef
43.
Byun JY, Yoon CH, An S, et al. The Rac1/MKK7/JNK pathway signals upregulation of Atg5 and subsequent autophagic cell death in response to oncogenic Ras. Carcinogenesis. 2009;30(11):1880–8.PubMedCrossRef
44.
Samatar AA, Poulikakos PI. Targeting RAS-ERK signalling in cancer: promises and challenges. Nat Rev Drug Discov. 2014;13(12):928–42.PubMedCrossRef
45.
Kochetkova EY, Blinova GI, Bystrova OA, et al. Suppression of mTORC1 activity in senescent Ras-transformed cells neither restores autophagy nor abrogates apoptotic death caused by inhibition of MEK/ERK kinases. Aging (Albany NY). 2018;10(11):3574–89.CrossRef
46.
Zhang X, Cheng Q, Yin H, et al. Regulation of autophagy and EMT by the interplay between p53 and RAS during cancer progression (review). Int J Oncol. 2017;51(1):18–24.PubMedCrossRef
47.
Qiu XY, Hu DX, Chen WQ, et al. PD-L1 confers glioblastoma multiforme malignancy via Ras binding and Ras/Erk/EMT activation. Biochim Biophys Acta Mol basis Dis. 2018;1864(5 Pt A):1754–69.PubMedCrossRef
48.
Wu D, Zhao B, Qi X, et al. Nogo-B receptor promotes epithelial-mesenchymal transition in non-small cell lung cancer cells through the Ras/ERK/Snail1 pathway. Cancer Lett. 2018;418:135–46.PubMedCrossRefPubMedCentral
49.
50.
Mulholland DJ, Kobayashi N, Ruscetti M, et al. Pten loss and RAS/MAPK activation cooperate to promote EMT and metastasis initiated from prostate cancer stem/progenitor cells. Cancer Res. 2012;72(7):1878–89.PubMedPubMedCentralCrossRef
51.
Zhang L, Wang H, Zhu J, et al. FTY720 reduces migration and invasion of human glioblastoma cell lines via inhibiting the PI3K/AKT/mTOR/p70S6K signaling pathway. Tumour Biol. 2014;35(11):10707–14.PubMedCrossRef
52.
Wang H, Zhang C, Xu L, et al. Bufalin suppresses hepatocellular carcinoma invasion and metastasis by targeting HIF-1alpha via the PI3K/AKT/mTOR pathway. Oncotarget. 2016;7(15):20193–208.PubMedPubMedCentral
53.
Jiao D, Wang J, Lu W, et al. Curcumin inhibited HGF-induced EMT and angiogenesis through regulating c-met dependent PI3K/Akt/mTOR signaling pathways in lung cancer. Mol Ther Oncolytics. 2016;3:16018.PubMedPubMedCentralCrossRef
54.
Ni J, Cozzi P, Hao J, et al. Epithelial cell adhesion molecule (EpCAM) is associated with prostate cancer metastasis and chemo/radioresistance via the PI3K/Akt/mTOR signaling pathway. Int J Biochem Cell Biol. 2013;45(12):2736–48.PubMedCrossRef
55.
Chang L, Graham PH, Hao J, et al. Acquisition of epithelial-mesenchymal transition and cancer stem cell phenotypes is associated with activation of the PI3K/Akt/mTOR pathway in prostate cancer radioresistance. Cell Death Dis. 2013;4:e875.PubMedPubMedCentralCrossRef
56.
Zi D, Zhou ZW, Yang YJ, et al. Danusertib induces apoptosis, cell cycle arrest, and autophagy but inhibits epithelial to mesenchymal transition involving PI3K/Akt/mTOR signaling pathway in human ovarian cancer cells. Int J Mol Sci. 2015;16(11):27228–51.PubMedPubMedCentralCrossRef
57.
Li JP, Yang YX, Liu QL, et al. The pan-inhibitor of Aurora kinases danusertib induces apoptosis and autophagy and suppresses epithelial-to-mesenchymal transition in human breast cancer cells. Drug Des Devel Ther. 2015;9:1027–62.PubMedPubMedCentral
58.
59.
Russell RC, Tian Y, Yuan H, et al. ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase. Nat Cell Biol. 2013;15(7):741–50.PubMedPubMedCentralCrossRef
60.
Zhou WH, Tang F, Xu J, et al. Low expression of Beclin 1, associated with high Bcl-xL, predicts a malignant phenotype and poor prognosis of gastric cancer. Autophagy. 2012;8(3):389–400.PubMedCrossRef
61.
Pattingre S, Tassa A, Qu X, et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell. 2005;122(6):927–39.CrossRefPubMed
62.
Li S, Zhang HY, Du ZX, et al. Induction of epithelial-mesenchymal transition (EMT) by Beclin 1 knockdown via posttranscriptional upregulation of ZEB1 in thyroid cancer cells. Oncotarget. 2016;7(43):70364–77.PubMedPubMedCentral
63.
Cicchini M, Chakrabarti R, Kongara S, et al. Autophagy regulator BECN1 suppresses mammary tumorigenesis driven by WNT1 activation and following parity. Autophagy. 2014;10(11):2036–52.PubMedPubMedCentralCrossRef
64.
Cai Z, Capoulade C, Moyret-Lalle C, et al. Resistance of MCF7 human breast carcinoma cells to TNF-induced cell death is associated with loss of p53 function. Oncogene. 1997;15(23):2817–26.PubMedCrossRef
65.
Shen H, Yin L, Deng G, et al. Knockdown of Beclin-1 impairs epithelial-mesenchymal transition of colon cancer cells. J Cell Biochem. 2018;119(8):7022–31.PubMedCrossRef
66.
Kenzelmann Broz D, Spano Mello S, Bieging KT, et al. Global genomic profiling reveals an extensive p53-regulated autophagy program contributing to key p53 responses. Genes Dev. 2013;27(9):1016–31.PubMedPubMedCentralCrossRef
67.
Kumar A, Singh UK, Chaudhary A. Targeting autophagy to overcome drug resistance in cancer therapy. Future Med Chem. 2015;7(12):1535–42.PubMedCrossRef
68.
Chang CJ, Chao CH, Xia W, et al. p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs. Nat Cell Biol. 2011;13(3):317–23.PubMedPubMedCentralCrossRef
69.
Kim T, Veronese A, Pichiorri F, et al. p53 regulates epithelial-mesenchymal transition through microRNAs targeting ZEB1 and ZEB2. J Exp Med. 2011;208(5):875–83.PubMedPubMedCentralCrossRef
70.
Wu CW, Peng ML, Yeh KT, et al. Inactivation of p53 in pterygium influence miR-200a expression resulting in ZEB1/ZEB2 up-regulation and EMT processing. Exp Eye Res. 2016;146:206–11.PubMedCrossRef
71.
Dong P, Karaayvaz M, Jia N, et al. Mutant p53 gain-of-function induces epithelial-mesenchymal transition through modulation of the miR-130b-ZEB1 axis. Oncogene. 2013;32(27):3286–95.PubMedCrossRef
72.
Huang W, Yu LF, Zhong J, et al. Stat3 is involved in angiotensin II-induced expression of MMP2 in gastric cancer cells. Dig Dis Sci. 2009;54(10):2056–62.PubMedCrossRef
73.
Xie TX, Wei D, Liu M, et al. Stat3 activation regulates the expression of matrix metalloproteinase-2 and tumor invasion and metastasis. Oncogene. 2004;23(20):3550–60.PubMedCrossRef
74.
Xiao J, Gong Y, Chen Y, et al. IL-6 promotes epithelial-to-mesenchymal transition of human peritoneal mesothelial cells possibly through the JAK2/STAT3 signaling pathway. Am J Physiol Renal Physiol. 2017;313(2):F310–8.PubMedCrossRef
75.
Liu SC, Huang CM, Bamodu OA, et al. Ovatodiolide suppresses nasopharyngeal cancer by targeting stem cell-like population, inducing apoptosis, inhibiting EMT and dysregulating JAK/STAT signaling pathway. Phytomedicine. 2018;56:269–78.PubMedCrossRef
76.
Maycotte P, Jones KL, Goodall ML, et al. Autophagy supports breast cancer stem cell maintenance by regulating IL6 secretion. Mol Cancer Res. 2015;13(4):651–8.PubMedPubMedCentralCrossRef
77.
Granato M, Rizzello C, Gilardini Montani MS, et al. Quercetin induces apoptosis and autophagy in primary effusion lymphoma cells by inhibiting PI3K/AKT/mTOR and STAT3 signaling pathways. J Nutr Biochem. 2017;41:124–36.PubMedCrossRef
78.
Ferraresi A, Phadngam S, Morani F, et al. Resveratrol inhibits IL-6-induced ovarian cancer cell migration through epigenetic up-regulation of autophagy. Mol Carcinog. 2017;56(3):1164–81.PubMedCrossRef
79.
Hu F, Zhao Y, Yu Y, et al. Docetaxel-mediated autophagy promotes chemoresistance in castration-resistant prostate cancer cells by inhibiting STAT3. Cancer Lett. 2018;416:24–30.PubMedCrossRef
80.
Canel M, Serrels A, Miller D, et al. Quantitative in vivo imaging of the effects of inhibiting integrin signaling via Src and FAK on cancer cell movement: effects on E-cadherin dynamics. Cancer Res. 2010;70(22):9413–22.PubMedPubMedCentralCrossRef
81.
Sheng W, Chen C, Dong M, et al. Calreticulin promotes EGF-induced EMT in pancreatic cancer cells via integrin/EGFR-ERK/MAPK signaling pathway. Cell Death Dis. 2017;8(10):e3147.PubMedPubMedCentralCrossRef
82.
Bravou V, Klironomos G, Papadaki E, et al. ILK over-expression in human colon cancer progression correlates with activation of beta-catenin, down-regulation of E-cadherin and activation of the Akt-FKHR pathway. J Pathol. 2006;208(1):91–9.PubMedCrossRef
83.
Feldkoren B, Hutchinson R, Rapoport Y, et al. Integrin signaling potentiates transforming growth factor-beta 1 (TGF-beta1) dependent down-regulation of E-cadherin expression - important implications for epithelial to mesenchymal transition (EMT) in renal cell carcinoma. Exp Cell Res. 2017;355(2):57–66.PubMedCrossRef
84.
Pang M, Wang H, Rao P, et al. Autophagy links beta-catenin and Smad signaling to promote epithelial-mesenchymal transition via upregulation of integrin linked kinase. Int J Biochem Cell Biol. 2016;76:123–34.PubMedCrossRef
85.
Sosa P, Alcalde-Estevez E, Plaza P, et al. Hyperphosphatemia promotes senescence of myoblasts by impairing autophagy through ilk overexpression, a possible mechanism involved in sarcopenia. Aging Dis. 2018;9(5):769–84.PubMedPubMedCentralCrossRef
86.
87.
Shin S, Im HJ, Kwon YJ, et al. Human steroid sulfatase induces Wnt/beta-catenin signaling and epithelial-mesenchymal transition by upregulating Twist1 and HIF-1alpha in human prostate and cervical cancer cells. Oncotarget. 2017;8(37):61604–17.PubMedPubMedCentralCrossRef
88.
Ha JH, Ward JD, Radhakrishnan R, et al. Lysophosphatidic acid stimulates epithelial to mesenchymal transition marker Slug/Snail2 in ovarian cancer cells via Galphai2, Src, and HIF1alpha signaling nexus. Oncotarget. 2016;7(25):37664–79.PubMedPubMedCentralCrossRef
89.
Lo HW, Hsu SC, Xia W, et al. Epidermal growth factor receptor cooperates with signal transducer and activator of transcription 3 to induce epithelial-mesenchymal transition in cancer cells via up-regulation of TWIST gene expression. Cancer Res. 2007;67(19):9066–76.PubMedPubMedCentralCrossRef
90.
Yu X, Zheng Y, Zhu X, et al. Osteopontin promotes hepatocellular carcinoma progression via the PI3K/AKT/Twist signaling pathway. Oncol Lett. 2018;16(4):5299–308.PubMedPubMedCentral
91.
92.
Qiang L, Zhao B, Ming M, et al. Regulation of cell proliferation and migration by p62 through stabilization of Twist1. Proc Natl Acad Sci U S A. 2014;111(25):9241–6.PubMedPubMedCentralCrossRef
93.
94.
95.
Cheng M, Xue H, Cao W, et al. Receptor for activated C kinase 1 (RACK1) promotes Dishevelled protein degradation via autophagy and antagonizes Wnt signaling. J Biol Chem. 2016;291(24):12871–9.PubMedPubMedCentralCrossRef
96.
Gao C, Cao W, Bao L, et al. Autophagy negatively regulates Wnt signalling by promoting Dishevelled degradation. Nat Cell Biol. 2010;12(8):781–90.PubMedCrossRef
97.
Ma B, Liu B, Cao W, et al. The Wnt signaling antagonist Dapper1 accelerates Dishevelled2 degradation via promoting its ubiquitination and aggregate-induced autophagy. J Biol Chem. 2015;290(19):12346–54.PubMedPubMedCentralCrossRef
98.
Zhang Y, Wang F, Han L, et al. GABARAPL1 negatively regulates Wnt/beta-catenin signaling by mediating Dvl2 degradation through the autophagy pathway. Cell Physiol Biochem. 2011;27(5):503–12.PubMedCrossRef
99.
Gugnoni M, Sancisi V, Gandolfi G, et al. Cadherin-6 promotes EMT and cancer metastasis by restraining autophagy. Oncogene. 2017;36(5):667–77.PubMedCrossRef
100.
Miao Y, Zhang Y, Chen Y, et al. GABARAP is overexpressed in colorectal carcinoma and correlates with shortened patient survival. Hepatogastroenterology. 2010;57(98):257–61.PubMed
101.
Huber MA, Kraut N, Beug H. Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol. 2005;17(5):548–458.PubMedCrossRef
102.
103.
Liu H, Xiong J, He T, et al. High uric acid-induced epithelial-mesenchymal transition of renal tubular epithelial cells via the TLR4/NF-kB signaling pathway. Am J Nephrol. 2017;46(4):333–42.PubMedCrossRef
104.
Cichon MA, Radisky DC. ROS-induced epithelial-mesenchymal transition in mammary epithelial cells is mediated by NF-kB-dependent activation of snail. Oncotarget. 2014;5(9):2827–38.PubMedPubMedCentralCrossRef
105.
Wu Y, Deng J, Rychahou PG, et al. Stabilization of snail by NF-kappaB is required for inflammation-induced cell migration and invasion. Cancer Cell. 2009;15(5):416–28.PubMedPubMedCentralCrossRef
106.
Nopparat C, Sinjanakhom P, Govitrapong P. Melatonin reverses H2 O2 -induced senescence in SH-SY5Y cells by enhancing autophagy via sirtuin 1 deacetylation of the RelA/p65 subunit of NF-kappaB. J Pineal Res. 2017;63(1).CrossRef
107.
Sun X, Li L, Ma HG, et al. Bisindolylmaleimide alkaloid BMA-155Cl induces autophagy and apoptosis in human hepatocarcinoma HepG-2 cells through the NF-kappaB p65 pathway. Acta Pharmacol Sin. 2017;38(4):524–38.PubMedPubMedCentralCrossRef
108.
He ZJ, Zhu FY, Li SS, et al. Inhibiting ROS-NF-kappaB-dependent autophagy enhanced brazilin-induced apoptosis in head and neck squamous cell carcinoma. Food Chem Toxicol. 2017;101:55–66.PubMedCrossRef
109.
Huang M, Xin W. Matrine inhibiting pancreatic cells epithelial-mesenchymal transition and invasion through ROS/NF-kappaB/MMPs pathway. Life Sci. 2018;192:55–61.PubMedCrossRef
110.
Katsuno Y, Lamouille S, Derynck R. TGF-beta signaling and epithelial-mesenchymal transition in cancer progression. Curr Opin Oncol. 2013;25(1):76–84.PubMedCrossRef
111.
Miyazono K. Transforming growth factor-beta signaling in epithelial-mesenchymal transition and progression of cancer. Proc Jpn Acad Ser B Phys Biol Sci. 2009;85(8):314–23.PubMedPubMedCentralCrossRef
112.
Li J, Yang B, Zhou Q, et al. Autophagy promotes hepatocellular carcinoma cell invasion through activation of epithelial-mesenchymal transition. Carcinogenesis. 2013;34(6):1343–51.PubMedCrossRef
113.
Zhu L, Fu X, Chen X, et al. M2 macrophages induce EMT through the TGF-beta/Smad2 signaling pathway. Cell Biol Int. 2017;41(9):960–8.PubMedCrossRef
114.
Carito V, Bonuccelli G, Martinez-Outschoorn UE, et al. Metabolic remodeling of the tumor microenvironment: migration stimulating factor (MSF) reprograms myofibroblasts toward lactate production, fueling anabolic tumor growth. Cell Cycle. 2012;11(18):3403–14.PubMedPubMedCentralCrossRef
115.
Saitoh M, Endo K, Furuya S, et al. STAT3 integrates cooperative Ras and TGF-beta signals that induce snail expression. Oncogene. 2016;35(8):1049–57.PubMedCrossRef
116.
Ma F, Li W, Liu C, et al. MiR-23a promotes TGF-beta1-induced EMT and tumor metastasis in breast cancer cells by directly targeting CDH1 and activating Wnt/beta-catenin signaling. Oncotarget. 2017;8(41):69538–50.PubMedPubMedCentralCrossRef
117.
118.
Shen J, Zhao DS, Li MZ. TGF-beta1 promotes human gastric carcinoma SGC7901 cells invasion by inducing autophagy. Eur Rev Med Pharmacol Sci. 2017;21(5):1013–9.PubMed
119.
Suzuki HI, Kiyono K, Miyazono K. Regulation of autophagy by transforming growth factor-beta (TGF-beta) signaling. Autophagy. 2010;6(5):645–7.PubMedCrossRef
120.
Zhang C, Zhang X, Xu R, et al. TGF-beta2 initiates autophagy via Smad and non-Smad pathway to promote glioma cells’ invasion. J Exp Clin Cancer Res. 2017;36(1):162.PubMedPubMedCentralCrossRef
121.
Hu S, Wang L, Zhang X, et al. Autophagy induces transforming growth factor-beta-dependent epithelial-mesenchymal transition in hepatocarcinoma cells through cAMP response element binding signalling. J Cell Mol Med. 2018;22(11):5518–32.PubMedPubMedCentralCrossRef
122.
Peng JM, Bera R, Chiou CY, et al. Actin cytoskeleton remodeling drives epithelial-mesenchymal transition for hepatoma invasion and metastasis in mice. Hepatology. 2018;67(6):2226–43.PubMedCrossRef
123.
Huang D, Cao L, Xiao L, et al. Hypoxia induces actin cytoskeleton remodeling by regulating the binding of CAPZA1 to F-actin via PIP2 to drive EMT in hepatocellular carcinoma. Cancer Lett. 2019;448:117–27.PubMedCrossRef
124.
Huang D, Cao L, Zheng S. CAPZA1 modulates EMT by regulating actin cytoskeleton remodelling in hepatocellular carcinoma. J Exp Clin Cancer Res. 2017;36(1):13.PubMedPubMedCentralCrossRef
125.
Aguilera MO, Beron W, Colombo MI. The actin cytoskeleton participates in the early events of autophagosome formation upon starvation induced autophagy. Autophagy. 2012;8(11):1590–603.PubMedPubMedCentralCrossRef
126.
127.
Kashatus JA, Nascimento A, Myers LJ, et al. Erk2 phosphorylation of Drp1 promotes mitochondrial fission and MAPK-driven tumor growth. Mol Cell. 2015;57(3):537–51.PubMedPubMedCentralCrossRef
128.
Serasinghe MN, Wieder SY, Renault TT, et al. Mitochondrial division is requisite to RAS-induced transformation and targeted by oncogenic MAPK pathway inhibitors. Mol Cell. 2015;57(3):521–36.PubMedPubMedCentralCrossRef
129.
130.
Gugnoni M, Sancisi V, Manzotti G, et al. Autophagy and epithelial-mesenchymal transition: an intricate interplay in cancer. Cell Death Dis. 2016;7(12):e2520.PubMedPubMedCentralCrossRef
131.
Shi C, Cai Y, Li Y, et al. Yap promotes hepatocellular carcinoma metastasis and mobilization via governing cofilin/F-actin/lamellipodium axis by regulation of JNK/Bnip3/SERCA/CaMK II pathways. Redox Biol. 2018;14:59–71.PubMedCrossRef
132.
Maes H, Van Eygen S, Krysko DV, et al. BNIP3 supports melanoma cell migration and vasculogenic mimicry by orchestrating the actin cytoskeleton. Cell Death Dis. 2014;5:e1127.PubMedPubMedCentralCrossRef
133.
Zhao Z, Zhao J, Xue J, et al. Autophagy inhibition promotes epithelial-mesenchymal transition through ROS/HO-1 pathway in ovarian cancer cells. Am J Cancer Res. 2016;6(10):2162–77.PubMedPubMedCentral
134.
Qin W, Li C, Zheng W, et al. Inhibition of autophagy promotes metastasis and glycolysis by inducing ROS in gastric cancer cells. Oncotarget. 2015;6(37):39839–54.PubMedPubMedCentralCrossRef
135.
Lv Q, Wang W, Xue J, et al. DEDD interacts with PI3KC3 to activate autophagy and attenuate epithelial-mesenchymal transition in human breast cancer. Cancer Res. 2012;72(13):3238–50.PubMedCrossRef
136.
Lv Q, Hua F, Hu ZW. DEDD, a novel tumor repressor, reverses epithelial-mesenchymal transition by activating selective autophagy. Autophagy. 2012;8(11):1675–6.PubMedPubMedCentralCrossRef
137.
Jiang GM, Tan Y, Wang H. The relationship between autophagy and the immune system and its applications for tumor immunotherapy. Mol Cancer. 2019;18(1):17.PubMedPubMedCentralCrossRef
138.
Ouyang F, Huang H, Zhang M, et al. HMGB1 induces apoptosis and EMT in association with increased autophagy following H/R injury in cardiomyocytes. Int J Mol Med. 2016;37(3):679–89.PubMedPubMedCentralCrossRef
139.
Li XF, Chen DP, Ouyang FZ, et al. Increased autophagy sustains the survival and pro-tumourigenic effects of neutrophils in human hepatocellular carcinoma. J Hepatol. 2015;62(1):131–9.PubMedCrossRef
140.
Lock R, Kenific CM, Leidal AM, et al. Autophagy-dependent production of secreted factors facilitates oncogenic RAS-driven invasion. Cancer Discov. 2014;4(4):466–79.PubMedPubMedCentralCrossRef
141.
Dash S, Sarashetti PM, Rajashekar B, et al. TGF-beta2-induced EMT is dampened by inhibition of autophagy and TNF-alpha treatment. Oncotarget. 2018;9(5):6433–49.PubMedPubMedCentralCrossRef
142.
Su Z, Li G, Liu C, et al. Autophagy inhibition impairs the epithelial-mesenchymal transition and enhances cisplatin sensitivity in nasopharyngeal carcinoma. Oncol Lett. 2017;13(6):4147–54.PubMedPubMedCentralCrossRef
143.
Tong H, Yin H, Hossain MA, et al. Starvation-induced autophagy promotes the invasion and migration of human bladder cancer cells via TGF-beta1/Smad3-mediated epithelial-mesenchymal transition activation. J Cell Biochem. 2019;120(4):5118–27.PubMedCrossRef
144.
Wang H, Zhang Y, Wu Q, et al. miR-16 mimics inhibit TGF-beta1-induced epithelial-to-mesenchymal transition via activation of autophagy in non-small cell lung carcinoma cells. Oncol Rep. 2018;39(1):247–54.PubMedCrossRef
145.
Jiang Y, Jiao Y, Liu Y, et al. Sinomenine hydrochloride inhibits the metastasis of human glioblastoma cells by suppressing the expression of matrix Metalloproteinase-2/−9 and reversing the endogenous and exogenous epithelial-mesenchymal transition. Int J Mol Sci. 2018;19(3). https://​doi.​org/​10.​3390/​ijms19030844.
146.
Wang Y, Liu Y, Lu J, et al. Rapamycin inhibits FBXW7 loss-induced epithelial-mesenchymal transition and cancer stem cell-like characteristics in colorectal cancer cells. Biochem Biophys Res Commun. 2013;434(2):352–6.PubMedPubMedCentralCrossRef
147.
Reka AK, Kuick R, Kurapati H, et al. Identifying inhibitors of epithelial-mesenchymal transition by connectivity map-based systems approach. J Thorac Oncol. 2011;6(11):1784–92.PubMedPubMedCentralCrossRef
148.
Ye R, Dai N, He Q, et al. Comprehensive anti-tumor effect of Brusatol through inhibition of cell viability and promotion of apoptosis caused by autophagy via the PI3K/Akt/mTOR pathway in hepatocellular carcinoma. Biomed Pharmacother. 2018;105:962–73.PubMedCrossRef
149.
Chen X, Chen Y, Lin X, et al. The drug combination of SB202190 and SP600125 significantly inhibit the growth and metastasis of Olaparib-resistant ovarian cancer cell. Curr Pharm Biotechnol. 2018;19(6):506–13.PubMedCrossRef
150.
Niu NK, Wang ZL, Pan ST, et al. Pro-apoptotic and pro-autophagic effects of the Aurora kinase a inhibitor alisertib (MLN8237) on human osteosarcoma U-2 OS and MG-63 cells through the activation of mitochondria-mediated pathway and inhibition of p38 MAPK/PI3K/Akt/mTOR signaling pathway. Drug Des Devel Ther. 2015;9:1555–84.PubMedPubMedCentral
151.
Liao H, Huang Y, Guo B, et al. Dramatic antitumor effects of the dual mTORC1 and mTORC2 inhibitor AZD2014 in hepatocellular carcinoma. Am J Cancer Res. 2015;5(1):125–39.PubMed
Metadata
Title
Crosstalk between autophagy and epithelial-mesenchymal transition and its application in cancer therapy
Authors
Hong-Tao Chen
Hao Liu
Min-Jie Mao
Yuan Tan
Xiang-Qiong Mo
Xiao-Jun Meng
Meng-Ting Cao
Chu-Yu Zhong
Yan Liu
Hong Shan
Guan-Min Jiang
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2019
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-019-1030-2

Other articles of this Issue 1/2019

Molecular Cancer 1/2019 Go to the issue

Research

Small Molecule KRAS Agonist for Mutant KRAS Cancer Therapy

Research

Novel long noncoding RNA OTUD6B-AS1 indicates poor prognosis and inhibits clear cell renal cell carcinoma proliferation via the Wnt/β-catenin signaling pathway

Letter to the Editor

RNA-Seq profiling of circular RNAs in human colorectal Cancer liver metastasis and the potential biomarkers

Review

Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance

Letter to the Editor

Circular RNA F-circSR derived from SLC34A2-ROS1 fusion gene promotes cell migration in non-small cell lung cancer

Research

Circ-AKT3 inhibits clear cell renal cell carcinoma metastasis via altering miR-296-3p/E-cadherin signals

2024 ASCO Annual Meeting Coverage

Highlights of the Day: Breast cancer – metastatic

Breast Cancer Video

In this session, Dr. Wolff provides his key takeaways from the data presented in the metastatic breast cancer oral abstract session at ASCO 2024.

Watch now

Highlights of the Day: Gynecologic cancer

Gynecologic Cancer Video

Highlights of the Day: Breast Cancer – local/regional/adjuvant

Breast Cancer Video

Neoadjuvant dual immunotherapy improves melanoma outcomes

04-06-2024 Melanoma News

» View more highlights on the ASCO 2024 congress hub page

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits