Leukaemia inhibitory factor in gastric cancer: friend or foe?
Cancer stem cells
Gastric cancer
Hippo/YAP pathway
JAK/STAT pathway
LIF
LIFRβ
Therapies
Journal
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
ISSN: 1436-3305
Titre abrégé: Gastric Cancer
Pays: Japan
ID NLM: 100886238
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
23
11
2021
accepted:
13
01
2022
pubmed:
3
2
2022
medline:
9
3
2022
entrez:
2
2
2022
Statut:
ppublish
Résumé
IL-6 family cytokine leukaemia inhibitory factor (LIF) study has deciphered a variety of effects, in physiology as well as pathology. Despite the sudden arousal in LIF interest in cancers, its study in the gastric cancer (GC) context has been put aside. Only few related studies can be found in literature, most of them investigating IL-6/STAT3 signalling in GC, and not the particular LIF/LIFRβ signalisation. LIF/LIFR has opposing effects depending on the signalling pathways involved. This review relates the pro- and anti-tumorigenic aspects of LIF/LIFR in GC, taking also into account facts from other types of cancer. A better understanding of these issues would undoubtedly help postulate interesting hypotheses and perspectives for future LIF/LIFR study and its use in GC therapies, where options tend to be limited in number and efficiency.
Identifiants
pubmed: 35106710
doi: 10.1007/s10120-022-01278-w
pii: 10.1007/s10120-022-01278-w
doi:
Substances chimiques
Leukemia Inhibitory Factor
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
299-305Informations de copyright
© 2022. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.
Références
Yue X, Wu L, Hu W. The regulation of leukemia inhibitory factor. Cancer Cell Microenviron. 2015;2:e877.
pubmed: 26807429
pmcid: 4722946
Gearing DP, Gough NM, King JA, Hilton DJ, Nicola NA, Simpson RJ, et al. Molecular cloning and expression of cDNA encoding a murine myeloid leukaemia inhibitory factor (LIF). EMBO J. 1987;6:3995–4002.
pubmed: 3127201
pmcid: 553879
Smith AG, Nichols J, Robertson M, Rathjen PD. Differentiation inhibiting activity (DIA/LIF) and mouse development. Dev Biol. 1992;151:339–51.
pubmed: 1601171
Moreau JF, Donaldson DD, Bennett F, Witek-Giannotti J, Clark SC, Wong GG. Leukaemia inhibitory factor is identical to the myeloid growth factor human interleukin for DA cells. Nature. 1988;336:690–2.
pubmed: 3143918
Rosario GX, Stewart CL. The multifaceted actions of leukaemia inhibitory factor in mediating uterine receptivity and embryo implantation. Am J Reprod Immunol. 2016;75:246–55.
pubmed: 26817565
Oshima K, Teo DTW, Senn P, Starlinger V, Heller S. LIF promotes neurogenesis and maintains neural precursors in cell populations derived from spiral ganglion stem cells. BMC Dev Biol. 2007;7:112.
pubmed: 17935626
pmcid: 2080640
Jia D, Cai M, Xi Y, Du S, Zhenjun T. Interval exercise training increases LIF expression and prevents myocardial infarction-induced skeletal muscle atrophy in rats. Life Sci. 2018;193:77–86.
pubmed: 29223542
Nicola NA, Babon JJ. Leukemia inhibitory factor (LIF). Cytokine Growth Factor Rev. 2015;26:533–44.
pubmed: 26187859
pmcid: 4581962
Jones SA, Jenkins BJ. Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer. Nat Rev Immunol. 2018;18:773–89.
pubmed: 30254251
Johnson DE, O’Keefe RA, Grandis JR. Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol. 2018;15:234–48.
pubmed: 29405201
pmcid: 5858971
Yu H, Lee H, Herrmann A, Buettner R, Jove R. Revisiting STAT3 signalling in cancer: new and unexpected biological functions. Nat Rev Cancer. 2014;14:736–46.
pubmed: 25342631
Giese B, Roderburg C, Sommerauer M, Wortmann SB, Metz S, Heinrich PC, et al. Dimerization of the cytokine receptors gp130 and LIFR analysed in single cells. J Cell Sci. 2005;118:5129–40.
pubmed: 16254248
Rodig SJ, Meraz MA, White JM, Lampe PA, Riley JK, Arthur CD, et al. Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses. Cell. 1998;93:373–83.
pubmed: 9590172
Pinho V, Fernandes M, da Costa A, Machado R, Gomes AC. Leukemia inhibitory factor: Recent advances and implications in biotechnology. Cytokine Growth Factor Rev. 2020;52:25–33.
pubmed: 31870618
Kershaw NJ, Murphy JM, Liau NPD, Varghese LN, Laktyushin A, Whitlock EL, et al. SOCS3 binds specific receptor-JAK complexes to control cytokine signaling by direct kinase inhibition. Nat Struct Mol Biol. 2013;20:469–76.
pubmed: 23454976
pmcid: 3618588
Kershaw NJ, Laktyushin A, Nicola NA, Babon JJ. Reconstruction of an active SOCS3-based E3 ubiquitin ligase complex in vitro: identification of the active components and JAK2 and gp130 as substrates. Growth Factors. 2014;32:1–10.
pubmed: 24438103
pmcid: 4085236
Li X, Yang Q, Yu H, Wu L, Zhao Y, Zhang C, et al. LIF promotes tumorigenesis and metastasis of breast cancer through the AKT-mTOR pathway. Oncotarget. 2014;5:788–801.
pubmed: 24553191
pmcid: 3996668
Ali SA, Kaur G, Kaushik JK, Malakar D, Mohanty AK, Kumar S. Examination of pathways involved in leukemia inhibitory factor (LIF)-induced cell growth arrest using label-free proteomics approach. J Proteom. 2017;168:37–52.
Chen D, Sun Y, Wei Y, Zhang P, Rezaeian AH, Teruya-Feldstein J, et al. LIFR is a breast cancer metastasis suppressor upstream of the Hippo-YAP pathway and a prognostic marker. Nat Med. 2012;18:1511–7.
pubmed: 23001183
pmcid: 3684419
Luo Q, Wang C, Jin G, Gu D, Wang N, Song J, et al. LIFR functions as a metastasis suppressor in hepatocellular carcinoma by negatively regulating phosphoinositide 3-kinase/AKT pathway. Carcinogenesis. 2015;36:1201–12.
pubmed: 26249360
Lei C, Lv S, Wang H, Liu C, Zhai Q, Wang S, et al. Leukemia inhibitory factor receptor suppresses the metastasis of clear cell renal cell carcinoma through negative regulation of the yes-associated protein. DNA Cell Biol. 2018;37:659–69.
pubmed: 29902078
Guo H, Cheng Y, Martinka M, McElwee K. High LIFr expression stimulates melanoma cell migration and is associated with unfavorable prognosis in melanoma. Oncotarget. 2015;6:25484–98.
pubmed: 26329521
pmcid: 4694846
Buckley AM, Lynam-Lennon N, Kennedy SA, Dunne MR, Aird JJ, Foley EK, et al. Leukaemia inhibitory factor is associated with treatment resistance in oesophageal adenocarcinoma. Oncotarget. 2018;9:33634–47.
pubmed: 30263091
pmcid: 6154751
Gulluoglu S, Sahin M, Tuysuz EC, Yaltirik CK, Kuskucu A, Ozkan F, et al. Leukemia inhibitory factor promotes aggressiveness of chordoma. Oncol Res. 2017;25:1177–88.
pubmed: 28247842
pmcid: 7841199
Ma D, Jing X, Shen B, Liu X, Cheng X, Wang B, et al. Leukemia inhibitory factor receptor negatively regulates the metastasis of pancreatic cancer cells in vitro and in vivo. Oncol Rep. 2016;36:827–36.
pubmed: 27375070
Shi Y, Gao W, Lytle NK, Huang P, Yuan X, Dann AM, et al. Targeting LIF-mediated paracrine interaction for pancreatic cancer therapy and monitoring. Nature. 2019;569:131–5.
pubmed: 30996350
pmcid: 6565370
Terawaki K, Sawada Y, Kashiwase Y, Hashimoto H, Yoshimura M, Suzuki M, et al. New cancer cachexia rat model generated by implantation of a peritoneal dissemination-derived human stomach cancer cell line. Am J Physiol Endocrinol Metab. 2014;306:E373-387.
pubmed: 24347053
Tye H, Kennedy CL, Najdovska M, McLeod L, McCormack W, Hughes N, et al. STAT3-driven upregulation of TLR2 promotes gastric tumorigenesis independent of tumor inflammation. Cancer Cell. 2012;22:466–78.
pubmed: 23079657
Judd LM, Bredin K, Kalantzis A, Jenkins BJ, Ernst M, Giraud AS. STAT3 activation regulates growth, inflammation, and vascularization in a mouse model of gastric tumorigenesis. Gastroenterology. 2006;131:1073–85.
pubmed: 17030178
Jackson CB, Judd LM, Menheniott TR, Kronborg I, Dow C, Yeomans ND, et al. Augmented gp130-mediated cytokine signalling accompanies human gastric cancer progression. J Pathol. 2007;213:140–51.
pubmed: 17724739
Fukui H, Watari J, Zhang X, Ran Y, Tomita T, Oshima T, et al. Phosphorylated STAT3 expression linked to SOCS3 methylation is associated with proliferative ability of gastric mucosa in patients with early gastric cancer. Oncol Lett. 2020;19:3542–50.
pubmed: 32269628
pmcid: 7115067
Zhang X-M, Zhou C, Gu H, Yan L, Zhang G-Y. Correlation of RKIP, STAT3 and cyclin D1 expression in pathogenesis of gastric cancer. Int J Clin Exp Pathol. 2014;7:5902–8.
pubmed: 25337233
pmcid: 4203204
Xiao C, Hong H, Yu H, Yuan J, Guo C, Cao H, et al. MiR-340 affects gastric cancer cell proliferation, cycle, and apoptosis through regulating SOCS3/JAK-STAT signaling pathway. Immunopharmacol Immunotoxicol. 2018;40:278–83.
pubmed: 29658372
Hanahan D, Coussens LM. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell. 2012;21:309–22.
Haykal MM, Nahmias C, Varon C, Martin OCB. Organotypic modeling of the tumor landscape. Front Cell Dev Biol. 2020;8:606039.
pubmed: 33330508
pmcid: 7732527
Wu X, Tao P, Zhou Q, Li J, Yu Z, Wang X, et al. IL-6 secreted by cancer-associated fibroblasts promotes epithelial-mesenchymal transition and metastasis of gastric cancer via JAK2/STAT3 signaling pathway. Oncotarget. 2017;8:20741–50.
pubmed: 28186964
pmcid: 5400541
Zhang F, Li K, Pan M, Li W, Wu J, Li M, et al. miR-589 promotes gastric cancer aggressiveness by a LIFR-PI3K/AKT-c-Jun regulatory feedback loop. J Exp Clin Cancer Res. 2018;37:152.
pubmed: 30012200
pmcid: 6048856
Zhao J-H, Sun J-X, Song Y-X, Chen X-W, Yang Y-C, Ma B, et al. A novel long noncoding RNA-LOWEG is low expressed in gastric cancer and acts as a tumor suppressor by inhibiting cell invasion. J Cancer Res Clin Oncol. 2016;142:601–9.
pubmed: 26537802
Nguyen PH, Giraud J, Chambonnier L, Dubus P, Wittkop L, Belleannée G, et al. Characterization of biomarkers of tumorigenic and chemoresistant cancer stem cells in human gastric carcinoma. Clin Cancer Res. 2017;23:1586–97.
pubmed: 27620279
Seeneevassen L, Bessède E, Mégraud F, Lehours P, Dubus P, Varon C. Gastric cancer: advances in carcinogenesis research and new therapeutic strategies. Int J Mol Sci. 2021;22:3418.
pubmed: 33810350
pmcid: 8037554
Nandy SB, Arumugam A, Subramani R, Pedroza D, Hernandez K, Saltzstein E, et al. MicroRNA-125a influences breast cancer stem cells by targeting leukemia inhibitory factor receptor which regulates the Hippo signaling pathway. Oncotarget. 2015;6:17366–78.
pubmed: 25962054
pmcid: 4627314
Molina Castro SE, Tiffon C, Giraud J, Boeuf H, Sifre E, Giese A, et al. The Hippo kinase LATS2 controls Helicobacter pylori-induced epithelial-mesenchymal transition and intestinal metaplasia in gastric mucosa. Cell Mol Gastroenterol Hepatol. 2020;9:257–76.
pubmed: 31669263
Giraud J, Molina-Castro S, Seeneevassen L, Sifré E, Izotte J, Tiffon C, et al. Verteporfin targeting YAP1/TAZ-TEAD transcriptional activity inhibits the tumorigenic properties of gastric cancer stem cells. Int J Cancer. 2019;146:2255–67.
pubmed: 31489619
Seeneevassen L, Giraud J, Molina-Castro S, Sifré E, Tiffon C, Beauvoit C, et al. Leukaemia inhibitory factor (LIF) inhibits cancer stem cells tumorigenic properties through hippo kinases activation in gastric cancer. Cancers (Basel). 2020;12:2011.
Xu G, Wang H, Li W, Xue Z, Luo Q. Leukemia inhibitory factor inhibits the proliferation of gastric cancer by inducing G1-phase arrest. J Cell Physiol. 2019;234:3613–20.
pubmed: 30565675
Kanda M, Nagai T, Takahashi T, Liu ML, Kondou N, Naito AT, et al. Leukemia inhibitory factor enhances endogenous cardiomyocyte regeneration after myocardial infarction. PLoS ONE. 2016;11: e0156562.
pubmed: 27227407
pmcid: 4881916
Welc SS, Flores I, Wehling-Henricks M, Ramos J, Wang Y, Bertoni C, et al. Targeting a therapeutic LIF transgene to muscle via the immune system ameliorates muscular dystrophy. Nat Commun. 2019;10:2788.
pubmed: 31243277
pmcid: 6594976
Zhang YS, Xin DE, Wang Z, Song X, Sun Y, Zou QC, et al. STAT4 activation by leukemia inhibitory factor confers a therapeutic effect on intestinal inflammation. EMBO J. 2019;38: e99595.
pubmed: 30770344
pmcid: 6418461
Davis ID, Kiers L, MacGregor L, Quinn M, Arezzo J, Green M, et al. A randomized, double-blinded, placebo-controlled phase II trial of recombinant human leukemia inhibitory factor (rhuLIF, emfilermin, AM424) to prevent chemotherapy-induced peripheral neuropathy. Clin Cancer Res. 2005;11:1890–8.
pubmed: 15756015
Rambam Health Care Campus. Comparison of LIF (Leukemia Inhibitory Factor) Level Between Neonates Who Are IUGR (Intra Uterine Growth Restriction) and Those Who Are AGA (Average for Gestational Age) [Internet]. clinicaltrials.gov; 2015 Aug. Report No.: NCT02518126. Available from: https://www.clinicaltrials.gov/ct2/show/NCT02518126
Rambam Health Care Campus. The Correlation Between LIF Levels in Cord Blood to Maternal Blood in Women Treated With Mg During Labor [Internet]. clinicaltrials.gov; 2015 Aug. Report No.: NCT02507817. Available from: https://www.clinicaltrials.gov/ct2/show/NCT02507817
Merck KGaA, Darmstadt, Germany. A Randomised, Double-blind, Placebo Controlled, Proof of Concept Study to Assess the Efficacy, Safety and Acceptability of r-hLIF for Improving Embryo Implantation Following in Vitro Fertilisation (IVF) and Embryo Transfer (ET) in Women With Recurrent Implantation Failure. [Internet]. clinicaltrials.gov; 2017 Jan. Report No.: NCT00504530. Available from: https://www.clinicaltrials.gov/ct2/show/NCT00504530
Merck KGaA, Darmstadt, Germany. A Multicentre, Randomised, Double-blind, Placebo-controlled Proof of Concept Study to Compare the Efficacy and Safety of r-hLIF (Emfilermin) for Improving Embryo Implantation Following in Vitro Fertilization (IVF) and Embryo Transfer (ET) in Women With Recurrent Implantation Failure [Internet]. clinicaltrials.gov; 2017 Jan. Report No.: NCT00504608. Available from: https://www.clinicaltrials.gov/ct2/show/NCT00504608
MD YG. The Correlation Between Gestational Age and Maternal and Fetal Levels of LIF and ACTH [Internet]. clinicaltrials.gov; 2017 Aug. Report No.: NCT03231904. Available from: https://www.clinicaltrials.gov/ct2/show/NCT03231904
Davis SM, Reichel D, Bae Y, Pennypacker KR. Leukemia inhibitory factor-loaded nanoparticles with enhanced cytokine metabolic stability and anti-inflammatory activity. Pharm Res. 2018;35:6.
pubmed: 29294201
pmcid: 6265655