Nasal allergen and methacholine provocation tests influence co‑expression patterns of TGF‑β/SMAD and MAPK signaling pathway genes in patients with asthma
- Authors:
- Jacek Plichta
- Alicja Majos
- Piotr Kuna
- Michał Panek
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Affiliations: Department of Internal Medicine, Asthma and Allergy, Medical University of Lodz, 90‑153 Lodz, Poland - Published online on: October 1, 2024 https://doi.org/10.3892/etm.2024.12735
- Article Number: 445
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Copyright: © Plichta et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
|
Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: A systematic analysis for the global burden of disease study 2019. GBD 2019 diseases and injuries collaborators. Lancet. 396:120–122. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Pelaia G, Vatrella A, Busceti MT, Gallelli L, Calabrese C, Terracciano R and Maselli R: Cellular mechanisms underlying eosinophilic and neutrophilic airway inflammation in asthma. Mediators Inflamm. 2015(879783)2015.PubMed/NCBI View Article : Google Scholar | |
|
Annunziato F, Romagnani C and Romagnani S: The 3 major types of innate and adaptive cell-mediated effector immunity. J Allergy Clin Immunol. 135:626–635. 2015.PubMed/NCBI View Article : Google Scholar | |
|
De Groot JC, Ten Brinke A and Bel EHD: Management of the patient with eosinophilic asthma: A new era begins. ERJ Open Res. 23(00024-2015)2015.PubMed/NCBI View Article : Google Scholar | |
|
Ozdemir C, Kucuksezer UC, Akdis M and Akdis CA: The concepts of asthma endotypes and phenotypes to guide current and novel treatment strategies. Expert Rev Respir Med. 12:733–743. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Lambrecht BN and Hammad H: The immunology of asthma. Nat Immunol. 16:45–56. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Svenningsen S and Nair P: Asthma endotypes and an overview of targeted therapy for asthma. Front Med. 26(158)2017.PubMed/NCBI View Article : Google Scholar | |
|
Kuruvilla ME, Lee FEH and Lee GB: Understanding asthma phenotypes, endotypes and mechanisms of disease. Clin Rev Allerg Immunol. 56:219–133. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Chiu CJ and Huang MT: Asthma in the precision medicine era: Biologics and probiotics. Int J Mol Sci. 22(4528)2019.PubMed/NCBI View Article : Google Scholar | |
|
Lötvall J, Akdis CA, Bacharier LB, Bjermer L, Casale TB, Custovic A, Robert F, Lemanske Jr, Wardlaw AJ, Wenzel SE and Greenberger PA: Asthma endotypes: A new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol. 127:355–360. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Jia CE, Zhang HP, Lv Y, Liang R, Jiang YQ, Powell H, Fu JJ, Wang L, Gibson PG and Wang G: The asthma control test and asthma control questionnaire for assessing asthma control: Systematic review and meta-analysis. J Allergy Clin Immunol. 131:695–703. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Reddel HK, FitzGerald JM, Bateman ED, Bacharier LB, Becker A, Brusselle G, Buhl R, Cruz AA, Fleming L, Inoue H, et al: GINA 2019: A fundamental change in asthma management: Treatment of asthma with short-acting bronchodilators alone is no longer recommended for adults and adolescents. Eur Resp J. 53(1901046)2019.PubMed/NCBI View Article : Google Scholar | |
|
Genuneit J, Cantelmo JL, Weinmayr G, Wong GWK, Cooper PJ, Riikjärv MA, Gotua M, Kabesch M, Mutius von E, Forastiere F, et al: A multi-centre study of candidate genes for wheeze and allergy: The international study of asthma and allergies in childhood phase 2: A multi-centre study of candidate genes for wheeze and allergy. Clin Exp Allergy. 39:1875–1888. 2009.PubMed/NCBI View Article : Google Scholar | |
|
Anderson GP: Endotyping asthma: New insights into key pathogenic mechanisms in a complex, heterogeneous disease. Lancet. 372:1107–1119. 2008.PubMed/NCBI View Article : Google Scholar | |
|
Wenzel SE: Asthma: Defining of the persistent adult phenotypes. Lancet. 368:804–813. 2006.PubMed/NCBI View Article : Google Scholar | |
|
Heldin CH and Moustakas A: Signaling receptors for TGF-β family members. Cold Spring Harb Perspect Biol. 8(a022053)2016.PubMed/NCBI View Article : Google Scholar | |
|
Lichtman MK, Otero-Vinas M and Falanga V: Transforming growth factor beta (TGF-β) isoforms in wound healing and fibrosis. Wound Repair Regen. 24:215–2122. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Travis MA and Sheppard D: TGF-β activation and function in immunity. Annu Rev Immunol. 32:51–82. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Munger JS and Sheppard D: Cross talk among TGF-Signaling pathways, integrins, and the extracellular matrix. Cold Spring Harbor Perspectives in Biology. 3:a005017. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Hinz B: The extracellular matrix and transforming growth factor-β1: Tale of a strained relationship. Matrix Biol. 47:54–65. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Peng D, Fu M, Wang M, Wei Y and Wei X: Targeting TGF-β signal transduction for fibrosis and cancer therapy. Mol Cancer. 21(104)2022.PubMed/NCBI View Article : Google Scholar | |
|
Hata A and Chen YG: TGF-β signaling from receptors to smads. Cold Spring Harb Perspect Biol. 8(a022061)2016.PubMed/NCBI View Article : Google Scholar | |
|
Vander Ark A, Cao J and Li X: TGF-β receptors: In and beyond TGF-β signaling. Cell Signal. 52:112–120. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Drabsch Y and Ten Dijke P: TGF-β signaling and its role in cancer progression and metastasis. Cancer Metastasis Rev. 31:553–568. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Huang T, David L, Mendoza V, MVillarreal YYM, De K, Sun LZ, Fang X, López-Casillas F, Wrana JL and Hinck AP: TGF-β signaling is mediated by two autonomously functioning TβRI:TβRII pairs: TGF-β signals through autonomous TβRI:TβRII pairs. The EMBO J. 30:1263–1276. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Tzavlaki K and Moustakas A: TGF-β signaling. Biomolecules. 10(487)2020.PubMed/NCBI View Article : Google Scholar | |
|
Xu P, Liu J and Derynck R: Post-translational regulation of TGF-β receptor and Smad signaling. FEBS Lett. 586:1871–1884. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Massagué J: TGFβ signaling in context. Nat Rev Mol Cell Biol. 13:616–630. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Aashaq S, Batool A, Mir SA, Beigh MA, Andrabi KI and Shah ZA: TGF-β signaling: A recap of SMAD-independent and SMAD-dependent pathways. J Cell Physiol. 237:59–85. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Derynck R and Zhang YE: Smad-dependent and Smad-independent pathways in TGF- beta family signaling. Nature. 425:577–584. 2003.PubMed/NCBI View Article : Google Scholar | |
|
Zhang YE: Non-Smad signaling pathways of the TGF-β family. Cold Spring Harb Perspect Biol. 9(a022129)2017.PubMed/NCBI View Article : Google Scholar | |
|
Zi Z, Chapnick DA and Liu X: Dynamics of TGF-β/Smad signaling. FEBS Letters. 586:1921–1928. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Deng Z, Fan T, Xiao C, Tian H, Zheng Y, Li C and He J: TGF-β signaling in health, disease, and therapeutics. Sig Transduct Target Ther. 9:1–40. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Tang J, Liu F, Cooper ME and Chai Z: Renal fibrosis as a hallmark of diabetic kidney disease: Potential role of targeting transforming growth factor-beta (TGF-β) and related molecules. Expert Opinion on Therapeutic Targets. 26:721–738. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Frangogiannis NG: Transforming growth factor-β in myocardial disease. Nat Rev Cardiol. 19:435–455. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Chakravarthy A, Khan L, Bensler NP, Bose P and De Carvalho DD: TGF-β-associated extracellular matrix genes link cancer-associated fibroblasts to immune evasion and immunotherapy failure. Nat Commun. 9(4692)2018.PubMed/NCBI View Article : Google Scholar | |
|
Mahmood MQ, Reid D, Ward C, Muller HK, Knight DA, Sohal SS and Walters EH: Transforming growth factor (TGF) β1 and Smad signaling pathways: A likely key to EMT-associated COPD pathogenesis. Respirology. 22:133–140. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Halwani R, Al-Muhsen S, Al-Jahdali H and Hamid Q: Role of transforming growth factor-β in airway remodeling in asthma. Am J Respir Cell Mol Biol. 44:127–133. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Meng XM, Tang PMK, Li J and Lan HY: TGF-β/Smad signaling in renal fibrosis. Front Physiol. 29(6)2015.PubMed/NCBI View Article : Google Scholar | |
|
Modi SJ and Kulkarni VM: Discovery of VEGFR-2 inhibitors exerting significant anticanceractivity against CD44+ and CD133+ cancer stem cells (CSCs): Reversal of TGF-β induced epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma. Eur J Med Chem. 207(112851)2020.PubMed/NCBI View Article : Google Scholar | |
|
Muraoka RS, Dumont N, Ritter CA, Dugger TC, Brantley DM, Chen J, Easterly E, Roebuck LR, Ryan S, Gotwals , et al: Blockade of TGF-beta inhibits mammary tumor cell viability, migration, and metastases. J Clin Invest. 109:1551–159. 2002.PubMed/NCBI View Article : Google Scholar | |
|
Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ, Adcock IM, Bateman ED, Bel EH, Bleecker ER, et al: International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 43:343–373. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Matricardi PM, Kleine-Tebbe J, Hoffmann HJ, Valenta R, Hilger C, Hofmaier S, Aalberse RC, Agache I, Asero R, Ballmer-Weber B, et al: EAACI molecular allergology user's guide. Pediatric Allergy and Immunol. 7 (Suppl):1–250. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar | |
|
Panek MG, Karbownik MS, Górski KM, Koćwin M, Kardas G, Marynowski M and Kuna P: New insights into the regulation of TGF-β/Smad and MPK signaling pathway gene expressions by nasal allergen and methacholine challenge test in asthma. Clin Transl Allergy. 12(e12172)2022.PubMed/NCBI View Article : Google Scholar | |
|
Yu HS, Angkasekwinai P, Chang SH, Chung Y and Dong C: Protease allergens induce the expression of IL-25 via Erk and p38 MAPK pathway. J Korean Med Sci. 25:829–834. 2010.PubMed/NCBI View Article : Google Scholar | |
|
Goumans MJ, Lebrin F and Valdimarsdottir G: Controlling the angiogenic switch. Trends Cardiovas Med. 13:301–307. 2003.PubMed/NCBI View Article : Google Scholar | |
|
Fredriksson K, Fielhaber JA, Lam JK, Yao X, Meyer KS, Keeran KJ, Zywicke GJ, Qu X, Yu ZX, Moss J, et al: Paradoxical effects of rapamycin on experimental house dust mite-induced asthma. PLoS One. 7(e33984)2012.PubMed/NCBI View Article : Google Scholar | |
|
Cockcroft DW, Killian DN, Mellon JJA and Hargreave FE: Bronchial reactivity to inhaled histamine: A method and clinical survey. Clin Exp Allergy. 7:235–243. 1977.PubMed/NCBI View Article : Google Scholar | |
|
Sumino K, Sugar EA, Irvin CG, Kaminsky DA, Shade D, Wei CY, Holbrook JT, Wise RA and Castro M: American Lung Association Asthma Clinical Research Centers. Methacholine challenge test: Diagnostic characteristics in asthmatic patients receiving controller medications. J Allergy Clin Immunol. 130:69–75. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American thoracic society was adopted by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med. 161:309–329. 2000. | |
|
Song WJ and Cho SH: Challenges in the management of asthma in the elderly. Allergy Asthma Immunol Res. 7:431–439. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Murray AB, Ferguson AC and Morrison B: Airway responsiveness to histamine as a test for overall severity of asthma in children. J Allergy Clin Immunol. 68:119–124. 1981.PubMed/NCBI View Article : Google Scholar | |
|
Davis BE and Cockcroft DW: Past, present and future uses of methacholine testing. Expert Rev Respir Med. 6:321–329. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Hewitt DJ: Interpretation of the ‘positive’ methacholine challenge. Am J Ind Med. 51:769–781. 2008.PubMed/NCBI View Article : Google Scholar | |
|
Woodruff PG, Dolganov GM, Ferrando RE, Donnelly S, Hays SR, Solberg OD, Carter R, Wong HH, Cadbury PS and Fahy JV: Hyperplasia of smooth muscle in mild to moderate asthma without changes in cell size or gene expression. Am J Respir Crit Care Med. 169:1001–1006. 2004.PubMed/NCBI View Article : Google Scholar | |
|
Mishra V, Banga J and Silveyra P: Oxidative stress and cellular pathways of asthma and inflammation: Therapeutic strategies and pharmacological targets. Pharmacol Ther. 181:169–182. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Hervás D, Rodriguez R and Garde J: Role of aeroallergen nasal challenge in asthmatic children. Allergolo Immunopathol. 39:17–22. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Gauvreau GM, Davis BE, Scadding G, Boulet LP, Bjermer L, Chaker L, Cockcroft DW, Dahlén B, Fokkens W, Hellings P, et al: Allergen provocation tests in respiratory research: Building on 50 years of experience. Eur Respir J. 60(2102782)2022.PubMed/NCBI View Article : Google Scholar | |
|
Eguiluz-Gracia I, Testera-Montes A, González M, Pérez-Sánchez N, Ariza N, Salas M, Moreno-Aguilar C, Campo P, Torres MJ and Rondon C: Safety and reproducibility of nasal allergen challenge. Allergy. 74:1125–1134. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Modena BD, Bleecker ER, Busse WW, Erzurum SC, Gaston BM, Jarjour NN, Meyers DA, Milosevic J, Tedrow JR, Wu W, et al: Gene expression correlated with severe asthma characteristics reveals heterogeneous mechanisms of severe disease. Am J Respir Crit Care Med. 195:1449–1463. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Fu JJ, Baines KJ, Wood LG and Gibson PG: Systemic inflammation is associated with differential gene expression and airway neutrophilia in asthma. J Integrative Biology. 17:187–199. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Peters MC, Mekonnen ZK, Yuan S, Bhakta NR, Woodruff PG and Fahy JV: Measures of gene expression in sputum cells can identify TH2-high and TH2-low subtypes of asthma. J Allergy Clin Immunol. 133:388–394. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Pelaia G, Gallelli L, D'Agostino B, Vatrella A, Cuda G, Fratto D, Renda T, Galderisi U, Piegari E, Crimi N, et al: Effects of TGF-β and glucocorticoids on map kinase phosphorylation, IL-6/IL-11 secretion and cell proliferation in primary cultures of human lung fibroblasts. J Cell Physiol. 210:489–497. 2007.PubMed/NCBI View Article : Google Scholar | |
|
Chen G and Khalil N: TGF-beta1 increases proliferation of airway smooth muscle cells by phosphorylation of map kinases. Respir Res. 7(2)2006.PubMed/NCBI View Article : Google Scholar | |
|
Gerthoffer WT and Singer CA: MAPK regulation of gene expression in airway smooth muscle. Respir Physiol Neurobiol. 137:237–250. 2003.PubMed/NCBI View Article : Google Scholar | |
|
Zentella A and Massague J: Transforming growth factor β induces myoblast differentiation in the presence of mitogens. Proc Natl Acad Sci U S A. 89:5176–5180. 1992.PubMed/NCBI View Article : Google Scholar | |
|
Tran DQ: TGF-β: The sword, the wand, and the shield of FOXP3+ regulatory T cells. J Mol Cell Biol. 4:29–37. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Tirado-Rodriguez B, Ortega E, Segura-Medina P and Huerta-Yepez S: TGF-β: An important mediator of allergic disease and a molecule with dual activity in cancer development. J Immunol Res. 2014(318481)2014.PubMed/NCBI View Article : Google Scholar | |
|
Hu HH, Chen DQ, Wang YN, Feng YL, Cao G, Vaziri ND and Zhao YY: New insights into TGF-β/Smad signaling in tissue fibrosis. Chem Biol Interact. 292:76–83. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Goumans MJ, Valdimarsdottir G, Itoh S, Rosendahl A, Sideras P and ten Dijke P: Balancing the activation state of the endothelium via two distinct TGF-beta type I receptors. EMBO J. 21:1743–1753. 2002.PubMed/NCBI View Article : Google Scholar | |
|
Schwartze JT, Becker S, Sakkas E, Wujak ŁA, Niess G, Usemann J, Reichenberger F, Herold S, Vadász I, Mayer K, et al: Glucocorticoids recruit Tgfbr3 and Smad1 to shift transforming growth factor-β signaling from the Tgfbr1/Smad2/3 axis to the Acvrl1/Smad1 axis in lung fibroblasts. J Biol Chem. 289:3262–3275. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Song B, Estrada KD and Lyons KM: Smad signaling in skeletal development and regeneration. Cytokin Growth Factor Rev. 20:379–388. 2009.PubMed/NCBI View Article : Google Scholar | |
|
Pelaia G, Cuda G, Vatrella A, Gallelli L, Caraglia M, Marra M, Abbruzzese A, Caputi M, Maselli R, et al: Mitogen-activated protein kinases and asthma. J Cell Physiol. 202:642–653. 2005.PubMed/NCBI View Article : Google Scholar | |
|
English J, Pearson G, Wilsbacher J, Swantek J, Karandikar M, Xu S and Cobb MH: New insights into the control of MAP kinase pathways. Exp Cell Res. 253:255–270. 1999.PubMed/NCBI View Article : Google Scholar | |
|
McCubrey JA, May WS, Duronio V and Mufson A: Serine/threonine phosphorylation in cytokine signal transduction. Leukemia. 14:9–21. 2000.PubMed/NCBI View Article : Google Scholar | |
|
Basaki Y, Ikizawa K, Kajiwara K and Yanagihara Y: CD40-mediated tumor necrosis factor receptor-associated factor 3 signaling upregulates IL-4-induced germline Cepsilon transcription in a human B cell line. Arch Biochem Biophys. 405:199–204. 2002.PubMed/NCBI View Article : Google Scholar | |
|
Kampen GT, Stafford S, Adachi T, Jinquan T, Quan S, Grant JA, Skov PS, Poulsen LK and Alam R: Eotaxin induces degranulation and chemotaxis of eosinophils through the activation of ERK2 and p38 mitogen-activated protein kinases. Blood. 95:1911–1917. 2000.PubMed/NCBI | |
|
Black JL and Johnson PRA: Factors controlling smooth muscle proliferation and airway remodelling. Curr Opin Allergy Clin Immunol. 2:47–51. 2002.PubMed/NCBI View Article : Google Scholar | |
|
Atherton HC, Jones G and Danahay H: IL-13-induced changes in the goblet cell density of human bronchial epithelial cell cultures: MAP kinase and phosphatidylinositol 3-kinase regulation. Am J Physiol Lung Cell Mol Physiol. 285:L730–L739. 2003.PubMed/NCBI View Article : Google Scholar | |
|
Pelaia C, Vatrella A, Crimi C, Gallelli L, Terracciano R and Pelaia G: Clinical relevance of understanding mitogen-activated protein kinases involved in asthma. Expert Rev Respir Med. 14:501–510. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Wortzel I and Seger R: The ERK cascade: Distinct functions within various subcellular organelles. Genes Cancer. 2:195–209. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Zou ML, Chen ZH, Teng YY, Liu SY, Jia Y, Zhang KW, Sun ZL, Wu JJ, Yuan JJ, Feng Y, et al: The Smad dependent TGF-β and BMP signaling pathway in bone remodeling and therapies. Front Mol Biosci. 8(593310)2021.PubMed/NCBI View Article : Google Scholar | |
|
Osman B, Doller A, Akool ES, Holdener M, Hintermann E, Pfeilschifter J and Eberhardt W: Rapamycin induces the TGFbeta1/Smad signaling cascade in renal mesangial cells upstream of mTOR. Cell Signal. 21:1806–1817. 2009.PubMed/NCBI View Article : Google Scholar | |
|
Halwani R, Sultana A, Vazquez-Tello A, Jamhawi A, Al-Masri AA and Al-Muhsen S: Th-17 regulatory cytokines IL-21, IL-23, and IL-6 enhance neutrophil production of IL-17 cytokines during asthma. J Asthma. 54:893–904. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Margelidon-Cozzolino V, Tsicopoulos A, Chenivesse C and de Nadai P: Role of Th17 cytokines in airway remodeling in asthma and therapy perspectives. Front Allergy. 3:2022.PubMed/NCBI View Article : Google Scholar | |
|
Aykul S, Maust J, Thamilselvan V, Floer M and Martinez-Hackert E: Smad2/3 activation regulates Smad1/5/8 signaling via a negative feedback loop to inhibit 3T3-L1 adipogenesis. Int J Mol Sci. 22(8472)2021.PubMed/NCBI View Article : Google Scholar | |
|
Morris JC, Tan AR, Olencki TE, Shapiro GI, Dezube BJ, Reiss M, Hsu FJ, Berzofsky JA and Lawrence DP: Phase I study of GC1008 (fresolimumab): A human anti-transforming growth factor-beta (TGFβ) monoclonal antibody in patients with advanced malignant melanoma or renal cell carcinoma. PLoS One. 9(e90353)2014.PubMed/NCBI View Article : Google Scholar | |
|
Reader CS, Vallath S, Steele CW, Haider S, Brentnall A, Desai A, Moore KM, Jamieson NB, Chang D, Bailey P, et al: The integrin αvβ6 drives pancreatic cancer through diverse mechanisms and represents an effective target for therapy. J Pathol. 249:332–342. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Moore KM, Thomas GJ, Duffy SW, Warwick J, Gabe R, Chou P, Ellis IO, Green AR, Haider S, Brouilette K, et al: Therapeutic targeting of integrin αvβ6 in breast cancer. J Natl Cancer Inst. 106(dju169)2014.PubMed/NCBI View Article : Google Scholar | |
|
Siljamäki E, Riihilä P, Suwal U, Nissinen L, Rappu P, Kallajoki M, Kähäri VM and Heino J: Inhibition of TGF-β signaling, invasion, and growth of cutaneous squamous cell carcinoma by PLX8394. Oncogene. 42:3633–347. 2023.PubMed/NCBI View Article : Google Scholar |
