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 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2021

Open Access 01-12-2021 | Metastasis | Review

ROS and TGFβ: from pancreatic tumour growth to metastasis

Authors: Chao-Hui Chang, Siim Pauklin

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2021

Login to get access

Abstract

Transforming growth factor β (TGFβ) signalling pathway switches between anti-tumorigenic function at early stages of cancer formation and pro-tumorigenic effects at later stages promoting cancer metastasis. A similar contrasting role has been uncovered for reactive oxygen species (ROS) in pancreatic tumorigenesis. Down-regulation of ROS favours premalignant tumour development, while increasing ROS level in pancreatic ductal adenocarcinoma (PDAC) enhances metastasis. Given the functional resemblance, we propose that ROS-mediated processes converge with the spatial and temporal activation of TGFβ signalling and thereby differentially impact early tumour growth versus metastatic dissemination. TGFβ signalling and ROS could extensively orchestrate cellular processes and this concerted function can be utilized by cancer cells to facilitate their malignancy. In this article, we revisit the interplay of canonical and non-canonical TGFβ signalling with ROS throughout pancreatic tumorigenesis and metastasis. We also discuss recent insight that helps to understand their conflicting effects on different stages of tumour development. These considerations open new strategies in cancer therapeutics.
Literature
1.
Batlle E, Massague J. Transforming Growth Factor-beta Signaling in Immunity and Cancer. Immunity. 2019;50(4):924–40.CrossRef
2.
Perillo B, Di Donato M, Pezone A, Di Zazzo E, Giovannelli P, Galasso G, et al. ROS in cancer therapy: the bright side of the moon. Exp Mol Med. 2020;52(2):192–203.CrossRef
3.
Durand N, Storz P. Targeting reactive oxygen species in development and progression of pancreatic cancer. Expert Rev Anticancer Ther. 2017;17(1):19–31.CrossRef
4.
Ogrunc M, Di Micco R, Liontos M, Bombardelli L, Mione M, Fumagalli M, et al. Oncogene-induced reactive oxygen species fuel hyperproliferation and DNA damage response activation. Cell Death Differ. 2014;21(6):998–1012.CrossRef
5.
O’Leary BR, Fath MA, Bellizzi AM, Hrabe JE, Button AM, Allen BG, et al. Loss of SOD3 (EcSOD) Expression Promotes an Aggressive Phenotype in Human Pancreatic Ductal Adenocarcinoma. Clin Cancer Res. 2015;21(7):1741–51.CrossRef
6.
Cheung EC, DeNicola GM, Nixon C, Blyth K, Labuschagne CF, Tuveson DA, et al. Dynamic ROS Control by TIGAR Regulates the Initiation and Progression of Pancreatic Cancer. Cancer Cell. 2020;37(2):168–82. e4.CrossRef
7.
Yoon YS, Lee JH, Hwang SC, Choi KS, Yoon G. TGF beta1 induces prolonged mitochondrial ROS generation through decreased complex IV activity with senescent arrest in Mv1Lu cells. Oncogene. 2005;24(11):1895–903.CrossRef
8.
Jain M, Rivera S, Monclus EA, Synenki L, Zirk A, Eisenbart J, et al. Mitochondrial reactive oxygen species regulate transforming growth factor-beta signaling. J Biol Chem. 2013;288(2):770–7.CrossRef
9.
Ishikawa F, Kaneko E, Sugimoto T, Ishijima T, Wakamatsu M, Yuasa A, et al. A mitochondrial thioredoxin-sensitive mechanism regulates TGF-beta-mediated gene expression associated with epithelial-mesenchymal transition. Biochem Biophys Res Commun. 2014;443(3):821–7.CrossRef
10.
Boudreau HE, Casterline BW, Rada B, Korzeniowska A, Leto TL. Nox4 involvement in TGF-beta and SMAD3-driven induction of the epithelial-to-mesenchymal transition and migration of breast epithelial cells. Free Radic Biol Med. 2012;53(7):1489–99.CrossRef
11.
Hiraga R, Kato M, Miyagawa S, Kamata T. Nox4-derived ROS signaling contributes to TGF-beta-induced epithelial-mesenchymal transition in pancreatic cancer cells. Anticancer Res. 2013;33(10):4431–8.
12.
Krstic J, Trivanovic D, Mojsilovic S, Santibanez JF. Transforming Growth Factor-Beta and Oxidative Stress Interplay: Implications in Tumorigenesis and Cancer Progression. Oxid Med Cell Longev. 2015;2015:654594.CrossRef
13.
Ahmad F, Ghosh S, Sinha S, Joshi SD, Mehta VS, Sen E. TGF-beta-induced hCG-beta regulates redox homeostasis in glioma cells. Mol Cell Biochem. 2015;399(1–2):105–12.CrossRef
14.
Patel AS, Lin L, Geyer A, Haspel JA, An CH, Cao J, et al. Autophagy in idiopathic pulmonary fibrosis. PLoS One. 2012;7(7):e41394.CrossRef
15.
Jobling MF, Mott JD, Finnegan MT, Jurukovski V, Erickson AC, Walian PJ, et al. Isoform-specific activation of latent transforming growth factor beta (LTGF-beta) by reactive oxygen species. Radiat Res. 2006;166(6):839–48.CrossRef
16.
Bellocq A, Azoulay E, Marullo S, Flahault A, Fouqueray B, Philippe C, et al. Reactive oxygen and nitrogen intermediates increase transforming growth factor-beta1 release from human epithelial alveolar cells through two different mechanisms. Am J Respir Cell Mol Biol. 1999;21(1):128–36.CrossRef
17.
Ayache N, Boumediene K, Mathy-Hartert M, Reginster JY, Henrotin Y, Pujol JP. Expression of TGF-betas and their receptors is differentially modulated by reactive oxygen species and nitric oxide in human articular chondrocytes. Osteoarthritis Cartilage. 2002;10(5):344–52.CrossRef
18.
Li WQ, Qureshi HY, Liacini A, Dehnade F, Zafarullah M. Transforming growth factor Beta1 induction of tissue inhibitor of metalloproteinases 3 in articular chondrocytes is mediated by reactive oxygen species. Free Radic Biol Med. 2004;37(2):196–207.CrossRef
19.
Fukawa T, Kajiya H, Ozeki S, Ikebe T, Okabe K. Reactive oxygen species stimulates epithelial mesenchymal transition in normal human epidermal keratinocytes via TGF-beta secretion. Exp Cell Res. 2012;318(15):1926–32.CrossRef
20.
Montorfano I, Becerra A, Cerro R, Echeverria C, Saez E, Morales MG, et al. Oxidative stress mediates the conversion of endothelial cells into myofibroblasts via a TGF-beta1 and TGF-beta2-dependent pathway. Lab Invest. 2014;94(10):1068–82.CrossRef
21.
Lin W, Tsai WL, Shao RX, Wu G, Peng LF, Barlow LL, et al. Hepatitis C virus regulates transforming growth factor beta1 production through the generation of reactive oxygen species in a nuclear factor kappaB-dependent manner. Gastroenterology. 2010;138(7):2509–18. 18 e1.CrossRef
22.
Latella G. Redox Imbalance in Intestinal Fibrosis: Beware of the TGFbeta-1, ROS, and Nrf2 Connection. Dig Dis Sci. 2018;63(2):312–20.CrossRef
23.
Witte D, Bartscht T, Kaufmann R, Pries R, Settmacher U, Lehnert H, et al. TGF-beta1-induced cell migration in pancreatic carcinoma cells is RAC1 and NOX4-dependent and requires RAC1 and NOX4-dependent activation of p38 MAPK. Oncol Rep. 2017;38(6):3693–701.
24.
Simeone DM, Zhang L, Graziano K, Nicke B, Pham T, Schaefer C, et al. Smad4 mediates activation of mitogen-activated protein kinases by TGF-beta in pancreatic acinar cells. Am J Physiol Cell Physiol. 2001;281(1):C311-9.CrossRef
25.
Lee MK, Pardoux C, Hall MC, Lee PS, Warburton D, Qing J, et al. TGF-beta activates Erk MAP kinase signalling through direct phosphorylation of ShcA. EMBO J. 2007;26(17):3957–67.CrossRef
26.
Son Y, Kim S, Chung HT, Pae HO. Reactive oxygen species in the activation of MAP kinases. Methods Enzymol. 2013;528:27–48.CrossRef
27.
Srinivas US, Tan BWQ, Vellayappan BA, Jeyasekharan AD. ROS and the DNA damage response in cancer. Redox Biol. 2019;25:101084.CrossRef
28.
Dabrowski A, Boguslowicz C, Dabrowska M, Tribillo I, Gabryelewicz A. Reactive oxygen species activate mitogen-activated protein kinases in pancreatic acinar cells. Pancreas. 2000;21(4):376–84.CrossRef
29.
Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008;321(5897):1801–6.CrossRef
30.
Seidler B, Schmidt A, Mayr U, Nakhai H, Schmid RM, Schneider G, et al. A Cre-loxP-based mouse model for conditional somatic gene expression and knockdown in vivo by using avian retroviral vectors. Proc Natl Acad Sci U S A. 2008;105(29):10137–42.CrossRef
31.
Olive KP, Tuveson DA. The use of targeted mouse models for preclinical testing of novel cancer therapeutics. Clin Cancer Res. 2006;12(18):5277–87.CrossRef
32.
Collins MA, Bednar F, Zhang Y, Brisset JC, Galban S, Galban CJ, et al. Oncogenic Kras is required for both the initiation and maintenance of pancreatic cancer in mice. J Clin Invest. 2012;122(2):639–53.CrossRef
33.
Principe DR, Diaz AM, Torres C, Mangan RJ, DeCant B, McKinney R, et al. TGFbeta engages MEK/ERK to differentially regulate benign and malignant pancreas cell function. Oncogene. 2017;36(30):4336–48.CrossRef
34.
Liou GY, Doppler H, DelGiorno KE, Zhang L, Leitges M, Crawford HC, et al. Mutant KRas-Induced Mitochondrial Oxidative Stress in Acinar Cells Upregulates EGFR Signaling to Drive Formation of Pancreatic Precancerous Lesions. Cell Rep. 2016;14(10):2325–36.CrossRef
35.
Al Saati T, Clerc P, Hanoun N, Peuget S, Lulka H, Gigoux V, et al. Oxidative stress induced by inactivation of TP53INP1 cooperates with KrasG12D to initiate and promote pancreatic carcinogenesis in the murine pancreas. Am J Pathol. 2013;182(6):1996–2004.CrossRef
36.
Collisson EA, Trejo CL, Silva JM, Gu S, Korkola JE, Heiser LM, et al. A central role for RAF–>MEK–>ERK signaling in the genesis of pancreatic ductal adenocarcinoma. Cancer Discov. 2012;2(8):685–93.CrossRef
37.
Binker MG, Binker-Cosen AA, Gaisano HY, de Cosen RH, Cosen-Binker LI. TGF-beta1 increases invasiveness of SW1990 cells through Rac1/ROS/NF-kappaB/IL-6/MMP-2. Biochem Biophys Res Commun. 2011;405(1):140–5.
38.
Su J, Morgani SM, David CJ, Wang Q, Er EE, Huang YH, et al. TGF-beta orchestrates fibrogenic and developmental EMTs via the RAS effector RREB1. Nature. 2020;577(7791):566–71.CrossRef
39.
Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324(5930):1029–33.CrossRef
40.
Folmes CD, Dzeja PP, Nelson TJ, Terzic A. Metabolic plasticity in stem cell homeostasis and differentiation. Cell Stem Cell. 2012;11(5):596–606.CrossRef
41.
Dmitrenko NP, Goroshnikova GV. [Metabolism of extracellular adenine nucleotides and adenosine uptake by rat thymocytes; the effect of concanavalin A]. Ukr Biokhim Zh (1978). 1987;59(2):61 – 5.
42.
Sosa V, Moline T, Somoza R, Paciucci R, Kondoh H, ME LL. Oxidative stress and cancer: an overview. Ageing Res Rev. 2013;12(1):376–90.CrossRef
43.
Zhao Y, Alakhova DY, Kabanov AV. Can nanomedicines kill cancer stem cells? Adv Drug Deliv Rev. 2013;65(13–14):1763–83.CrossRef
44.
Diehn M, Cho RW, Lobo NA, Kalisky T, Dorie MJ, Kulp AN, et al. Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature. 2009;458(7239):780–3.CrossRef
45.
Ye XQ, Wang GH, Huang GJ, Bian XW, Qian GS, Yu SC. Heterogeneity of mitochondrial membrane potential: a novel tool to isolate and identify cancer stem cells from a tumor mass? Stem Cell Rev Rep. 2011;7(1):153–60.CrossRef
46.
Ye XQ, Li Q, Wang GH, Sun FF, Huang GJ, Bian XW, et al. Mitochondrial and energy metabolism-related properties as novel indicators of lung cancer stem cells. Int J Cancer. 2011;129(4):820–31.CrossRef
47.
Heddleston JM, Li Z, Lathia JD, Bao S, Hjelmeland AB, Rich JN. Hypoxia inducible factors in cancer stem cells. Br J Cancer. 2010;102(5):789–95.CrossRef
48.
Koong AC, Mehta VK, Le QT, Fisher GA, Terris DJ, Brown JM, et al. Pancreatic tumors show high levels of hypoxia. Int J Radiat Oncol Biol Phys. 2000;48(4):919–22.CrossRef
49.
Vaupel P, Hockel M, Mayer A. Detection and characterization of tumor hypoxia using pO2 histography. Antioxid Redox Signal. 2007;9(8):1221–35.CrossRef
50.
Zhang Q, Han Z, Zhu Y, Chen J, Li W. Role of hypoxia inducible factor-1 in cancer stem cells (Review). Mol Med Rep. 2021;23(1):17.
51.
Rosell-Garcia T, Palomo-Alvarez O, Rodriguez-Pascual F. A hierarchical network of hypoxia-inducible factor and SMAD proteins governs procollagen lysyl hydroxylase 2 induction by hypoxia and transforming growth factor beta1. J Biol Chem. 2019;294(39):14308–18.CrossRef
52.
Ye J, Wu D, Wu P, Chen Z, Huang J. The cancer stem cell niche: cross talk between cancer stem cells and their microenvironment. Tumour Biol. 2014;35(5):3945–51.CrossRef
53.
Zhao H, Wu S, Li H, Duan Q, Zhang Z, Shen Q, et al. ROS/KRAS/AMPK Signaling Contributes to Gemcitabine-Induced Stem-like Cell Properties in Pancreatic Cancer. Mol Ther Oncolytics. 2019;14:299–312.CrossRef
54.
Hu Y, Lu W, Chen G, Wang P, Chen Z, Zhou Y, et al. K-ras(G12V) transformation leads to mitochondrial dysfunction and a metabolic switch from oxidative phosphorylation to glycolysis. Cell Res. 2012;22(2):399–412.CrossRef
55.
Pouyssegur J, Dayan F, Mazure NM. Hypoxia signalling in cancer and approaches to enforce tumour regression. Nature. 2006;441(7092):437–43.CrossRef
56.
Rohwer N, Cramer T. Hypoxia-mediated drug resistance: novel insights on the functional interaction of HIFs and cell death pathways. Drug Resist Updat. 2011;14(3):191–201.CrossRef
57.
Scortegagna M, Ding K, Oktay Y, Gaur A, Thurmond F, Yan LJ, et al. Multiple organ pathology, metabolic abnormalities and impaired homeostasis of reactive oxygen species in Epas1-/- mice. Nat Genet. 2003;35(4):331–40.CrossRef
58.
Holmquist-Mengelbier L, Fredlund E, Lofstedt T, Noguera R, Navarro S, Nilsson H, et al. Recruitment of HIF-1alpha and HIF-2alpha to common target genes is differentially regulated in neuroblastoma: HIF-2alpha promotes an aggressive phenotype. Cancer Cell. 2006;10(5):413–23.CrossRef
59.
Li Z, Bao S, Wu Q, Wang H, Eyler C, Sathornsumetee S, et al. Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell. 2009;15(6):501–13.CrossRef
60.
Branco-Price C, Zhang N, Schnelle M, Evans C, Katschinski DM, Liao D, et al. Endothelial cell HIF-1alpha and HIF-2alpha differentially regulate metastatic success. Cancer Cell. 2012;21(1):52–65.CrossRef
61.
Liu J, Wang Z. Increased Oxidative Stress as a Selective Anticancer Therapy. Oxid Med Cell Longev. 2015;2015:294303.CrossRef
62.
Laklai H, Miroshnikova YA, Pickup MW, Collisson EA, Kim GE, Barrett AS, et al. Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular fibrosis and tumor progression. Nat Med. 2016;22(5):497–505.CrossRef
63.
Erkan M, Michalski CW, Rieder S, Reiser-Erkan C, Abiatari I, Kolb A, et al. The activated stroma index is a novel and independent prognostic marker in pancreatic ductal adenocarcinoma. Clin Gastroenterol Hepatol. 2008;6(10):1155–61.CrossRef
64.
Menke A, Adler G. TGFbeta-induced fibrogenesis of the pancreas. Int J Gastrointest Cancer. 2002;31(1–3):41–6.CrossRef
65.
Yoo BM, Yeo M, Oh TY, Choi JH, Kim WW, Kim JH, et al. Amelioration of pancreatic fibrosis in mice with defective TGF-beta signaling. Pancreas. 2005;30(3):e71-9.CrossRef
66.
Vogelmann R, Ruf D, Wagner M, Adler G, Menke A. Effects of fibrogenic mediators on the development of pancreatic fibrosis in a TGF-beta1 transgenic mouse model. Am J Physiol Gastrointest Liver Physiol. 2001;280(1):G164-72.CrossRef
67.
Nagashio Y, Ueno H, Imamura M, Asaumi H, Watanabe S, Yamaguchi T, et al. Inhibition of transforming growth factor beta decreases pancreatic fibrosis and protects the pancreas against chronic injury in mice. Lab Invest. 2004;84(12):1610–8.CrossRef
68.
Phillips PA, McCarroll JA, Park S, Wu MJ, Pirola R, Korsten M, et al. Rat pancreatic stellate cells secrete matrix metalloproteinases: implications for extracellular matrix turnover. Gut. 2003;52(2):275–82.CrossRef
69.
Shek FW, Benyon RC, Walker FM, McCrudden PR, Pender SL, Williams EJ, et al. Expression of transforming growth factor-beta 1 by pancreatic stellate cells and its implications for matrix secretion and turnover in chronic pancreatitis. Am J Pathol. 2002;160(5):1787–98.CrossRef
70.
Masamune A, Watanabe T, Kikuta K, Satoh K, Shimosegawa T. NADPH oxidase plays a crucial role in the activation of pancreatic stellate cells. Am J Physiol Gastrointest Liver Physiol. 2008;294(1):G99–108.CrossRef
71.
Xia D, Halder B, Godoy C, Chakraborty A, Singla B, Thomas E, et al. NADPH oxidase 1 mediates caerulein-induced pancreatic fibrosis in chronic pancreatitis. Free Radic Biol Med. 2020;147:139–49.CrossRef
72.
Ozdemir BC, Pentcheva-Hoang T, Carstens JL, Zheng X, Wu CC, Simpson TR, et al. Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival. Cancer Cell. 2014;25(6):719–34.CrossRef
73.
Rhim AD, Oberstein PE, Thomas DH, Mirek ET, Palermo CF, Sastra SA, et al. Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma. Cancer Cell. 2014;25(6):735–47.CrossRef
74.
Chen Y, Kim J, Yang S, Wang H, Wu CJ, Sugimoto H, et al. Type I collagen deletion in alphaSMA(+) myofibroblasts augments immune suppression and accelerates progression of pancreatic cancer. Cancer Cell. 2021;39(4):548-65.
75.
Mojsilovic S, Mojsilovic SS, Bjelica S, Santibanez JF. ‘Transforming Growth Factor-Beta1 and Myeloid-Derived Suppressor Cells: A Cancerous Partnership’. Dev Dyn. 2021. Online ahead of print.
76.
Gonzalez-Junca A, Driscoll KE, Pellicciotta I, Du S, Lo CH, Roy R, et al. Autocrine TGFbeta Is a Survival Factor for Monocytes and Drives Immunosuppressive Lineage Commitment. Cancer Immunol Res. 2019;7(2):306–20.CrossRef
77.
Wei J, Zhang M, Zhou J. Myeloid-derived suppressor cells in major depression patients suppress T-cell responses through the production of reactive oxygen species. Psychiatry Res. 2015;228(3):695–701.CrossRef
78.
Centuori SM, Trad M, LaCasse CJ, Alizadeh D, Larmonier CB, Hanke NT, et al. Myeloid-derived suppressor cells from tumor-bearing mice impair TGF-beta-induced differentiation of CD4 + CD25 + FoxP3 + Tregs from CD4 + CD25-FoxP3- T cells. J Leukoc Biol. 2012;92(5):987–97.CrossRef
79.
Liyanage UK, Goedegebuure PS, Moore TT, Viehl CT, Moo-Young TA, Larson JW, et al. Increased prevalence of regulatory T cells (Treg) is induced by pancreas adenocarcinoma. J Immunother. 2006;29(4):416–24.CrossRef
80.
Clark CE, Hingorani SR, Mick R, Combs C, Tuveson DA, Vonderheide RH. Dynamics of the immune reaction to pancreatic cancer from inception to invasion. Cancer Res. 2007;67(19):9518–27.CrossRef
81.
Wang X, Lang M, Zhao T, Feng X, Zheng C, Huang C, et al. Cancer-FOXP3 directly activated CCL5 to recruit FOXP3(+)Treg cells in pancreatic ductal adenocarcinoma. Oncogene. 2017;36(21):3048–58.CrossRef
82.
Fu S, Zhang N, Yopp AC, Chen D, Mao M, Chen D, et al. TGF-beta induces Foxp3 + T-regulatory cells from CD4 + CD25 - precursors. Am J Transplant. 2004;4(10):1614–27.CrossRef
83.
Moo-Young TA, Larson JW, Belt BA, Tan MC, Hawkins WG, Eberlein TJ, et al. Tumor-derived TGF-beta mediates conversion of CD4 + Foxp3 + regulatory T cells in a murine model of pancreas cancer. J Immunother. 2009;32(1):12–21.CrossRef
84.
Kim HR, Lee A, Choi EJ, Hong MP, Kie JH, Lim W, et al. Reactive oxygen species prevent imiquimod-induced psoriatic dermatitis through enhancing regulatory T cell function. PLoS One. 2014;9(3):e91146.CrossRef
85.
Storz P, KRas. ROS and the initiation of pancreatic cancer. Small GTPases. 2017;8(1):38–42.CrossRef
86.
Gorrini C, Harris IS, Mak TW. Modulation of oxidative stress as an anticancer strategy. Nat Rev Drug Discov. 2013;12(12):931–47.CrossRef
87.
Suzuki S, Okada M, Shibuya K, Seino M, Sato A, Takeda H, et al. JNK suppression of chemotherapeutic agents-induced ROS confers chemoresistance on pancreatic cancer stem cells. Oncotarget. 2015;6(1):458–70.CrossRef
88.
Lo M, Ling V, Low C, Wang YZ, Gout PW. Potential use of the anti-inflammatory drug, sulfasalazine, for targeted therapy of pancreatic cancer. Curr Oncol. 2010;17(3):9–16.CrossRef
89.
Badgley MA, Kremer DM, Maurer HC, DelGiorno KE, Lee HJ, Purohit V, et al. Cysteine depletion induces pancreatic tumor ferroptosis in mice. Science. 2020;368(6486):85–9.CrossRef
Metadata
Title
ROS and TGFβ: from pancreatic tumour growth to metastasis
Authors
Chao-Hui Chang
Siim Pauklin
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2021
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-021-01960-4

Other articles of this Issue 1/2021

Journal of Experimental & Clinical Cancer Research 1/2021 Go to the issue

Review

The Anterior GRadient (AGR) family proteins in epithelial ovarian cancer

Research

A 5′-tRNA halve, tiRNA-Gly promotes cell proliferation and migration via binding to RBM17 and inducing alternative splicing in papillary thyroid cancer

Research

LncRNA CARMN overexpression promotes prognosis and chemosensitivity of triple negative breast cancer via acting as miR143-3p host gene and inhibiting DNA replication

Correction

Correction to: Natural product triptolide induces GSDME-mediated pyroptosis in head and neck cancer through suppressing mitochondrial hexokinase-ΙΙ

Research

HMGA1-TRIP13 axis promotes stemness and epithelial mesenchymal transition of perihilar cholangiocarcinoma in a positive feedback loop dependent on c-Myc

Research

ZIP10 drives osteosarcoma proliferation and chemoresistance through ITGA10-mediated activation of the PI3K/AKT pathway
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