Yang J, Antin P, Berx G, Blanpain C, Brabletz T, Bronner M, et al. Guidelines and definitions for research on epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 2020;21:341–52.
Thiery JP, Acloque H, Huang RYJ, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139:871–90.
Sisto M, Ribatti D, Lisi S. Organ fibrosis and autoimmunity: the role of inflammation in TGFβ-dependent EMT. Biomolecules. 2021;11:310.
Heerboth S, Housman G, Leary M, Longacre M, Byler S, Lapinska K, et al. EMT and tumor metastasis. Clin Transl Med. 2015;4:6.
Zeisberg M, Neilson EG. Biomarkers for epithelial-mesenchymal transitions. J Clin Invest. 2009;119:1429–37.
Stone RC, Pastar I, Ojeh N, Chen V, Liu S, Garzon KI, et al. Epithelial-mesenchymal transition in tissue repair and fibrosis. Cell Tissue Res. 2016;365:495–506.
Leggett SE, Hruska AM, Guo M, Wong IY. The epithelial-mesenchymal transition and the cytoskeleton in bioengineered systems. Cell Commun Signal. 2021;19:32.
Grigore AD, Jolly MK, Jia D, Farach-Carson MC, Levine H. Tumor budding: the name is EMT Partial EMT. J Clin Med. 2016;5:51.
Jolly MK, Ware KE, Gilja S, Somarelli JA, Levine H. EMT and MET: necessary or permissive for metastasis? Mol Oncol. 2017;11:755–69.
Aiello NM, Kang Y. Context-dependent EMT programs in cancer metastasis. J Exp Med. 2019;216:1016–26.
Nieto MA, Huang RYJ, Jackson RA, Thiery JPEMT. Cell. 2016;2016(166):21–45.
Sheng L, Zhuang S. New insights into the role and mechanism of partial epithelial-mesenchymal transition in kidney fibrosis. Front Physiol. 2020;11:569322.
Willis BC, Liebler JM, Luby-Phelps K, Nicholson AG, Crandall ED, du Bois RM, et al. Induction of epithelial-mesenchymal transition in alveolar epithelial cells by transforming growth factor-β1: potential role in idiopathic pulmonary fibrosis. Am J Pathol. 2005;166:1321–32.
Jolly MK, Boareto M, Huang B, Jia D, Lu M, Ben-Jacob E, et al. Implication of the hybrid epithelial/mesenchymal phenotype in metastasis. Front Oncol. 2015;5:155.
Aggarwal V, Montoya CA, Donnenberg VS, Sant S. Interplay between microenvironment and partial EMT as the driver of tumor progression. iScience. 2021;24:102113.
Papadaki MA, Stoupis G, Theodoropoulos PA, Mavroudis D, Georgoulias V, Agelaki S. Circulating tumor cells with stemness and epithelial-to-mesenchymal transition features are chemoresistant and predictive of poor outcome in metastatic breast cancer. Mol Cancer Ther. 2019;18:437–47.
Sun SC. The non-canonical NF-κB pathway in immunity and inflammation. Nat Rev Immunol. 2017;17:545–58.
López-Novoa JM, Nieto MA. Inflammation and EMT: an alliance towards organ fibrosis and cancer progression. EMBO Mol Med. 2009;1:303–14.
Suarez-Carmona M, Lesage J, Cataldo D, Gilles C. EMT and inflammation: inseparable actors of cancer progression. Mol Oncol. 2017;11:805–23.
Julien S, Puig I, Caretti E, Bonaventure J, Nelles L, van Roy F, et al. Activation of NF-κB by Akt upregulates Snail expression and induces epithelium mesenchyme transition. Oncogene. 2007;26:7445–56.
Yadav A, Kumar B, Datta J, Teknos TN, Kumar P. IL-6 promotes head and neck tumor metastasis by inducing epithelial-mesenchymal transition via the JAK-STAT3-SNAIL signaling pathway. Mol Cancer Res. 2011;9:1658–67.
Fernando RI, Castillo MD, Litzinger M, Hamilton DH, Palena C. IL-8 signaling plays a critical role in the epithelial-mesenchymal transition of human carcinoma cells. Cancer Res. 2011;71:5296–306.
Fu XT, Dai Z, Song K, Zhang ZJ, Zhou ZJ, Zhou SL, et al. Macrophage-secreted IL-8 induces epithelial-mesenchymal transition in hepatocellular carcinoma cells by activating JAK2/STAT3/Snail pathway. Int J Oncol. 2015;46:587–96.
Deng F, Weng Y, Li X, Wang T, Fan M, Shi Q. Overexpression of IL-8 promotes cell migration via PI3K-Akt signaling pathway and EMT in triple-negative breast cancer. Pathol Res Pract. 2020;216:15292.
Tabei Y, Yokota K, Nakajima Y. Interleukin-1β released from macrophages stimulated with indium tin oxide nanoparticles induced epithelial mesenchymal transition in A549 cells. Environ Sci Nano. 2022;9:1489–508.
Li Y, Wang L, Pappan L, Galliher-Beckley A, Shi J. IL-1β promotes stemness and invasiveness of colon cancer cells through Zeb1 activation. Mol Cancer. 2012;11:87.
Lee CH, Chang JSM, Syu SH, Wong TS, Chan JYW, Tang YC, et al. IL-1β promotes malignant transformation and tumor aggressiveness in oral cancer. J Cell Physiol. 2015;230:875–84.
Li R, Ong SL, Tran LM, Jing Z, Liu B, Park SJ, et al. Chronic IL-1β-induced inflammation regulates epithelial-to-mesenchymal transition memory phenotypes via epigenetic modifications in non-small cell lung cancer. Sci Rep. 2020;10:377.
Fang Z, Grütter C, Rauh D. Strategies for the selective regulation of kinases with allosteric modulators: exploiting exclusive structural features. ACS Chem Biol. 2013;8:58–70.
Harris VM. Protein detection by Simple Western™ analysis. Methods Mol Biol. 2015;1312:465–8.
Tabei Y, Abe H, Suzuki S, Takeda N, Arai JI, Nakajima Y. Sedanolide activates KEAP1-NRF2 pathway and ameliorates hydrogen peroxide-induced apoptotic cell death. Int J Mol Sci. 2023;24:16532.
Pastushenko I, Blanpain C. EMT transition state during tumor progression and metastasis. Trends Cell Biol. 2019;29:212–26.
Willis BC, Borok Z. TGF-beta-induced EMT: mechanisms and implications for fibrotic lung disease. Am J Physiol Lung Cell Mol Physiol. 2007;293:L525–35.
Weber A, Wasiliew P, Kracht M. Interleukin-1 (IL-1) pathway. Sci Signal. 2010;3:cm1.
Cheng CY, Kuo CT, Lin CC, Hsieh HL, Yang CM. IL-1beta induces expression of matrix metalloproteinase-9 and cell migration via a c-Src-dependent, growth factor receptor transactivation in A549 cells. Br J Pharmacol. 2010;160:1595–610.
Goh LK, Sorkin A. Endocytosis of receptor tyrosine kinase. Cold Spring Harb Perspect Biol. 2013;5:a017459.
Sanchez-Guerrero E, Chen E, Kockx M, An SW, Chong BH, Khachigian LM. IL-1beta signals through the EGF receptor and activates Egr-1 through MMP-ADAM. PLoS ONE. 2012;7:e39811.
Gialeli C, Theocharis AD, Karamanos NK. Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. FEBS J. 2011;278:16–27.
Liu Q, Yu S, Zhao W, Qin S, Chu Q, Wu K. EGFR-TKIs resistance via EGFR-independent signaling pathways. Mol Cancer. 2018;17:53.
Yotsumoto F, Fukagawa S, Miyata K, Nam SO, Katsuda T, Miyahara D, et al. HB-EGF is a promising therapeutic target for lung cancer with secondary mutation of EGFRT790M. Anticancer Res. 2017;37:3825–31.
Dinarello CA. Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol. 2009;27:519–50.
Pearson G, Robinson F, Gibson TB, Xu BE, Karandikar M, Berman K, et al. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev. 2001;22:153–83.
Fu L, Chen S, He G, Chen Y, Liu B. Targeting extracellular signal-regulated protein kinase 1/2 (ERK1/2) in cancer: An update on pharmacological small-molecule inhibitors. J Med Chem. 2022;65:13561–73.
Gantke T, Sriskantharajah S, Sadowski M, Ley SC. IκB kinase regulation of the TPL-2/ERK MAPK pathway. Immunol Rev. 2012;246:168–82.
Ben-Addi A, Mambole-Dema A, Brender C, Martin SR, Janzen J, Kjaer S, Smerdon SJ, et al. IκB kinase-induced interaction of TPL-2 kinase with 14-3-3 is essential for Toll-like receptor activation of ERK-1 and -2 MAP kinases. Proc Natl Acad Sci U S A. 2014;111:E2394–403.
Gonzalez DM, Medici D. Signaling mechanisms of the epithelial-mesenchymal transition. Sci Signal. 2014;7:re8.
Zhang J, Tian XJ, Zhang H, Teng Y, Li R, Bai F. TGF-β-induced epithelial-to-mesenchymal transition proceeds through stepwise activation of multiple feedback loops. Sci Signal. 2014;7:ra91.
Liarte S, Bernabé-García Á, Nicolás FJ. Human skin keratinocytes on sustained TGF-β stimulation reveal partial EMT features and weaken growth arrest responses. Cells. 2020;9:255.
Lundgren K, Nordenskjöld B, Landberg G. Hypoxia, Snail and incomplete epithelial-mesenchymal transition in breast cancer. Br J Cancer. 2009;101:1769–81.
Villanueva-Duque A, Zuniga-Eulogio MD, Dena-Beltran J, Castaneda-Saucedo E, Calixto-Galvez M, Mendoza-Catalán MA, et al. Leptin induces partial epithelial-mesenchymal transition in a FAK-ERK dependent pathway in MCF10A mammary non-tumorigenic cell. Int J Clin Exp Pathol. 2017;10:10334–42.
Hackel PO, Zwick E, Prenzel N, Ullrich A. Epidermal growth factor receptors: critical mediators of multiple receptor pathways. Curr Opin Cell Biol. 1999;11:184–9.
Moghal N, Sternberg PW. Multiple positive and negative regulators of signaling by the EGF-receptor. Curr Opin Cell Biol. 1999;11:190–6.
Zandi R, Larsen AB, Andersen P, Stockhausen MT, Poulsen HS. Mechanisms for oncogenic activation of the epidermal growth factor receptor. Cell Signal. 2007;19:2013–23.
Chen J, Zeng F, Forrester SJ, Eguchi S, Zhang MZ, Harris RC. Expression and function of the epidermal growth factor receptor in physiology and disease. Physiol Rev. 2016;96:1025–69.
Hynes NE, MacDonald G. ErbB receptors and signaling pathways in cancer. Curr Opin Cell Biol. 2009;21:177–84.
Higashiyama S, Nanba D, Nakayama H, Inoue H, Fukuda S. Ectodomain shedding and remnant peptide signaling of EGFRs and their ligands. J Biochem. 2011;150:15–22.
Liebmann C. EGF receptor activation by GPCRs: an universal pathway reveals different versions. Mol Cell Endocrinol. 2011;331:222–31.
Matsuo M, Sakurai H, Ueno Y, Ohtani O, Saiki I. Activation of MEK/ERK and PI3K/Akt pathways by fibronectin requires integrin αv-mediated ADAM activity in hepatocellalr carcinoma: a novel functional target for gefitinib. Cancer Sci. 2006;97:155–62.
Vara JAF, Casado E, de Castro J, Cejas P, Belda-Iniesta C, González-Barón M. PI3K/Akt signaling pathway and cancer. Cancer Treat Rev. 2004;30:193–204.
Larue L, Bellacosa A. Epithelial-mesenchymal transition in development and cancer: role of phosphatidylinositol 3’ kinase/AKT pathways. Oncogene. 2005;24:7443–54.
Maharati A, Moghbeli M. PI3K/AKT signaling pathway as a critical regulator of epithelial-mesenchymal transition in colorectal tumor cells. Cell Commun Signal. 2023;21:201.
Wang H, Wang HS, Zhou BH, Li CL, Zhang F, Wang XF, et al. Epithelial-mesenchymal transition (EMT) induced by TNF-α requires AKT/GSK-3β-mediated stabilization of snail in colorectal cancer. PLoS ONE. 2013;8:e56664.
Chang L, Graham PH, Hao J, Ni J, Bucci J, Cozzi PJ, 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.
Chen S, Yang Y, Zheng Z, Zhang M, Chen X, Xiao N, et al. IL-1β promotes esophageal squamous cell carcinoma growth and metastasis through FOXO3A by activating the PI3K/AKT pathway. Cell Death Discov. 2024;10:238.
Jaramillo ML, Banville M, Collins C, Paul-Roc B, Bourget L, O’Connor-McCourt M. Differential sensitivity of A549 non-small lung carcinoma cell responses to epidermal growth factor receptor pathway inhibitors. Cancer Biol Ther. 2008;7:557–68.
Liu ZC, Chen XH, Song HX, Wang HS, Zhang G, Wang H, et al. Snail regulated by PKC/GSK-3β pathway is crucial for EGF-induced epithelial-mesenchymal transition (EMT) of cancer cells. Cell Tissue Res. 2014;358:491–502.
Lauand C, Rezende-Teixeira P, Cortez BA, Niero EL, Machado-Santelli GM. Independent of ErbB1 gene copy number, EGF stimulates migration but not associated with cell proliferation in non-small cell lung cancer. Cancer Cell Int. 2013;13:38.
Schelch K, Vogel L, Schneller A, Brankovic J, Mohr T, Mayer RL, et al. EGF induces migration independent of EMT or invasion in A549 lung adenocarcinoma cells. Front Cell Dev Biol. 2021;9:634371.
Gasse P, Mary C, Guenon I, Noulin N, Charron S, Schnyder-Candrian S, et al. IL-1R1/MyD88 signaling and the inflammasome are essential in pulmonary inflammation and fibrosis in mice. J Clin Invest. 2007;117:3786–99.
Yang W, Bai X, Luan X, Min J, Tian X, Li H, et al. Delicate regulation of IL-1β-mediated inflammation by cyclophilin A. Cell Rep. 2022;38:110513.
Zou M, Zhang G, Zou J, Liu Y, Liu B, Hu X, et al. Inhibition of the ERK1/2-ubiquitas calpains pathway attenuates experimental pulmonary fibrosis in vivo and in vitro. Exp Cell Res. 2020;391: 111886.
Shaul YD, Seger R. The MEK/ERK cascade: from signaling specificity to diverse functions. Biochim Biophys Acta. 2007;1773:1213–26.
Yang L, Zheng L, Chng WJ, Ding JL. Comprehensive analysis of ERK1/2 substrates for potential combination immunotherapies. Trends Pharmacol Sci. 2019;40:897–910.
Tripathi K, Garg M. Mechanistic regulation of epithelial-to-mesenchymal transition through RAS signaling pathway and therapeutic implication in human cancer. J Cell Commun Signal. 2018;12:513–27.
Martin-Vega A, Cobb MH. Navigating the ERK1/2 MAPK cascade. Biomolecules. 2023;13:1555.
Rodríguez C, Pozo M, Nieto E, Fernández M, Alemany S. TRAF6 and Src kinase activity regulates Cot activation by IL-1. Cell Signal. 2006;18:1376–85.
Xu D, Matsumoto ML, McKenzie BS, Zarrin AA. TPL2 kinase action and control of inflammation. Pharmacol Res. 2018;129:188–93.
Perugorria MJ, Murphy LB, Fullard N, Chakraborty JB, Vyrla D, Wilson CL, et al. Tumor progression locus 2/Cot is required for activation of extracellular regulated kinase in liver injury and toll-like receptor-induced TIMP-1 gene transcription in hepatic stellate cells in mice. Hepatology. 2013;57:1238–49.
Kim K, Kim G, Kim JY, Yun HJ, Lim SC, Coi HS, et al. Interleukin-22 promotes epithelial cell transformation and breast tumorigenesis via MAP3K8 activation. Carcinogenesis. 2014;35:1352–61.
Lee HW, Cho HJ, Lee SJ, Song LH, Cho HJ, Park MC, et al. Tpl2 induces castration resistant prostate cancer progression and metastasis. Int J Cancer. 2015;136:2065–77.
Huber MA, Azoitei N, Baumann B, Grünert S, Sommer A, Pehamberger H, et al. NF-κB is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression. J Clin Invest. 2004;114:569–81.
Li Q, Li Z, Luo T, Shi H. Targeting the PI3K/AKT/mTOR and RAF/MEK/ERK pathways for cancer therapy. Mol Biomed. 2022;3:47.
De Luca A, Maiello MR, D’Alessio A, Pergameno M, Normanno N. The RAS/RAF/MEK/ERK and the PI3K/AKT signaling pathways: role in cancer pathogenesis and implications for therapeutic approaches. Expert Opin Ther Targets. 2012;16(Suppl 2):S17-27.
Cao Z, Liao Q, Su M, Huang K, Jin J, Cao D. AKT and ERK dual inhibitors: The way forward? Cancer Lett. 2019;459:30–40.
Ruhul Amin ARM, Senga T, Oo ML, Thant AA, Hamaguchi M. Secretion of matrix metalloproteinase-9 by the proinflammatory cytokine, IL-1β: a role for the dual signalling pathways. Akt and Erk Genes Cells. 2003;8:515–23.
Mendoza MC, Er EE, Blenis J. The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation. Trends Biochem Sci. 2011;36:320–8.
Pacold ME, Suire S, Peerisic O, Lara-Gonzalez S, Davis CT, Walker EH, et al. Crystal structure and functional analysis f Ras binding to its effector phosphoinositide 3-kinase γ. Cell. 2000;103:931–43.
Zimmermann S, Moelling K. Phosphorylation and regulation of Raf by Akt (protein kinase B). Science. 1999;286:1741–4.
Dodhiawala PB, Khurana N, Zhang D, Cheng Y, Li Lin, Wei Q, et al. TPL2 enforces RAS-induced inflammatory signaling and is activated by point mutations. J Clin Invest. 2020;130:4771–90.
Waterfield M, Jin W, Reiley W, Zhang M, Sun SC. IκB kinase is an essential component of the Tpl2 signaling pathway. Mol Cell Biol. 2004;24:6040–8.
He Y, Sun MM, Zhang GG, Yang J, Chen KS, Xu WW, et al. Targeting PI3K/Akt signal transduction for cancer therapy. Signal Transduct Target Ther. 2021;6:425.
Add Comment