STAT3 mediates RCP-induced cancer cell invasion through the NF-κB/Slug/MT1-MMP signaling cascade.
Cancer cell invasion
MT1-MMP
Rab coupling protein
STAT3
Slug
Journal
Archives of pharmacal research
ISSN: 1976-3786
Titre abrégé: Arch Pharm Res
Pays: Korea (South)
ID NLM: 8000036
Informations de publication
Date de publication:
Jul 2022
Jul 2022
Historique:
received:
16
03
2022
accepted:
24
06
2022
pubmed:
10
7
2022
medline:
29
7
2022
entrez:
9
7
2022
Statut:
ppublish
Résumé
Rab coupling protein (RCP) has been known to induce cancer invasion and metastasis, and STAT3 is one of major oncogenic factors. In the present study, we identify the critical role of STAT3 in RCP-induced cancer cell invasion. Immunohistochemical data of ovarian cancer tissues presented that levels of RCP expression are closely correlated with those of phospho-STAT3 (p-STAT3). In addition, ovarian cancer patients with high expression of both RCP and p-STAT3 had significantly lower progress-free and overall survival rates compared to those with low either RCP or p-STAT3 expression. Mechanistically, RCP induced STAT3 phosphorylation in both ovarian and breast cancer cells. Silencing or pharmacological inhibition of STAT3 significantly inhibited RCP-induced cancer cell invasion. In addition, we provide evidence that the β1 integrin/EGFR axis is important for RCP-induced STAT3 phosphorylation. Furthermore, STAT3 activated NF-κB for Slug expression that in turn upregulated MT1-MMP expression for cancer cell invasion. Collectively, our present data demonstrate that STAT3 is located downstream of the β1 integrin/EGFR axis and induces Slug and MT1-MMP expression for cancer cell invasion.
Identifiants
pubmed: 35809175
doi: 10.1007/s12272-022-01396-0
pii: 10.1007/s12272-022-01396-0
doi:
Substances chimiques
Integrin beta1
0
NF-kappa B
0
SNAI1 protein, human
0
STAT3 Transcription Factor
0
STAT3 protein, human
0
Snail Family Transcription Factors
0
ErbB Receptors
EC 2.7.10.1
Matrix Metalloproteinase 14
EC 3.4.24.80
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
460-474Subventions
Organisme : National research foundation of Korea
ID : NRF-2017R1E1A1A01074091
Organisme : National research foundation of Korea
ID : NRF-2022R1A2C1004019
Informations de copyright
© 2022. The Pharmaceutical Society of Korea.
Références
Berek JS, Kehoe ST, Kumar L, Friedlander M (2018) Cancer of the ovary, fallopian tube, and peritoneum. Int J Gynaecol Obstet 143(Suppl 2):59–78. https://doi.org/10.1002/ijgo.12614
doi: 10.1002/ijgo.12614
pubmed: 30306591
Chaffer CL, San Juan BP, Lim E, Weinberg RA (2016) EMT, cell plasticity and metastasis. Cancer Metastasis Rev 35:645–654. https://doi.org/10.1007/s10555-016-9648-7
doi: 10.1007/s10555-016-9648-7
pubmed: 27878502
Chesnelong C, Hao X, Cseh O, Wang AY, Luchman HA, Weiss S (2019) SLUG directs the precursor state of human brain tumor stem cells. Cancers (basel) 11:1635–1661. https://doi.org/10.3390/cancers11111635
doi: 10.3390/cancers11111635
Cho KH, Lee HY (2019) Rab25 and RCP in cancer progression. Arch Pharm Res 42:101–112. https://doi.org/10.1007/s12272-019-01129-w
doi: 10.1007/s12272-019-01129-w
pubmed: 30761451
Cho ES, Kang HE, Kim NH, Yook JI (2019a) Therapeutic implications of cancer epithelial-mesenchymal transition (EMT). Arch Pharm Res 42:14–24. https://doi.org/10.1007/s12272-018-01108-7
doi: 10.1007/s12272-018-01108-7
pubmed: 30649699
Cho KH, Jeong BY, Park CG, Lee HY (2019b) The YB-1/EZH2/amphiregulin signaling axis mediates LPA-induced breast cancer cell invasion. Arch Pharm Res 42:519–530. https://doi.org/10.1007/s12272-019-01149-6
doi: 10.1007/s12272-019-01149-6
pubmed: 31004257
Choe SR, Kim YN, Park CG, Cho KH, Cho DY, Lee HY (2018) RCP induces FAK phosphorylation and ovarian cancer cell invasion with inhibition by curcumin. Exp Mol Med 50:1–10. https://doi.org/10.1038/s12276-018-0078-1
doi: 10.1038/s12276-018-0078-1
pubmed: 29700289
Choi J, Lim H, Nam DK, Kim HS, Cho DY, Yi JW, Kim HC, Cho YK, Kim MW, Joo HJ, Lee KB, Kim KB (2001) Expression of thymidylate synthase in gastric cancer patients treated with 5-fluorouracil and doxorubicin-based adjuvant chemotherapy after curative resection. Br J Cancer 84:186–192. https://doi.org/10.1054/bjoc.2000.1553
doi: 10.1054/bjoc.2000.1553
pubmed: 11161374
pmcid: 2363711
Dai Y, Liu Y, Huang D, Yu C, Cai G, Pi L, Ren C, Chen GZ, Tian Y, Zhang X (2012) Increased expression of Rab coupling protein in squamous cell carcinoma of the head and neck and its clinical significance. Oncol Lett 3:1231–1236. https://doi.org/10.3892/ol.2012.652
doi: 10.3892/ol.2012.652
pubmed: 22783424
pmcid: 3392568
Dechow TN, Pedranzini L, Leitch A, Leslie K, Gerald WL, Linkov I, Bromberg JF (2004) Requirement of matrix metalloproteinase-9 for the transformation of human mammary epithelial cells by Stat3-C. Proc Natl Acad Sci U S A 101:10602–10607. https://doi.org/10.1073/pnas.0404100101
doi: 10.1073/pnas.0404100101
pubmed: 15249664
pmcid: 489981
Furtek SL, Backos DS, Matheson CJ, Reigan P (2016) Strategies and approaches of targeting STAT3 for cancer treatment. ACS Chem Biol 11:308–318. https://doi.org/10.1021/acschembio.5b00945
doi: 10.1021/acschembio.5b00945
pubmed: 26730496
Gao H, Teng C, Huang W, Peng J, Wang C (2015) SOX2 promotes the epithelial to mesenchymal transition of esophageal squamous cells by modulating slug expression through the activation of STAT3/HIF-alpha signaling. Int J Mol Sci 16:21643–21657. https://doi.org/10.3390/ijms160921643
doi: 10.3390/ijms160921643
pubmed: 26370982
pmcid: 4613272
Homsi J, Cubitt C, Daud A (2007) The Src signaling pathway: a potential target in melanoma and other malignancies. Expert Opin Ther Targets 11:91–100. https://doi.org/10.1517/14728222.11.1.91
doi: 10.1517/14728222.11.1.91
pubmed: 17150037
Hwang MH, Cho KH, Jeong KJ, Park YY, Kim JM, Yu SL, Park CG, Mills GB, Lee HY (2017) RCP induces slug expression and cancer cell invasion by stabilizing beta1 integrin. Oncogene 36:1102–1111. https://doi.org/10.1038/onc.2016.277
doi: 10.1038/onc.2016.277
pubmed: 27524413
Jacquemet G, Green DM, Bridgewater RE, von Kriegsheim A, Humphries MJ, Norman JC, Caswell PT (2013) RCP-driven alpha5beta1 recycling suppresses Rac and promotes RhoA activity via the RacGAP1-IQGAP1 complex. J Cell Biol 202:917–935. https://doi.org/10.1083/jcb.201302041
doi: 10.1083/jcb.201302041
pubmed: 24019536
pmcid: 3776348
Kim BH, Yi EH, Ye SK (2016) Signal transducer and activator of transcription 3 as a therapeutic target for cancer and the tumor microenvironment. Arch Pharm Res 39:1085–1099. https://doi.org/10.1007/s12272-016-0795-8
doi: 10.1007/s12272-016-0795-8
pubmed: 27515050
Kim JY, Cho KH, Jeong BY, Park CG, Lee HY (2020) Zeb1 for RCP-induced oral cancer cell invasion and its suppression by resveratrol. Exp Mol Med 52:1152–1163. https://doi.org/10.1038/s12276-020-0474-1
doi: 10.1038/s12276-020-0474-1
pubmed: 32728068
pmcid: 8080807
Lee H, Herrmann A, Deng JH, Kujawski M, Niu G, Li Z, Forman S, Jove R, Pardoll DM, Yu H (2009) Persistently activated STAT3 maintains constitutive NF-kappaB activity in tumors. Cancer Cell 15:283–293. https://doi.org/10.1016/j.ccr.2009.02.015
doi: 10.1016/j.ccr.2009.02.015
pubmed: 19345327
pmcid: 2777654
Liu S, Sun J, Cai B, Xi X, Yang L, Zhang Z, Feng Y, Sun Y (2016) NANOG regulates epithelial-mesenchymal transition and chemoresistance through activation of the STAT3 pathway in epithelial ovarian cancer. Tumour Biol 37:9671–9680. https://doi.org/10.1007/s13277-016-4848-x
doi: 10.1007/s13277-016-4848-x
pubmed: 26801672
Lo HW, Hsu SC, Xia W, Cao X, Shih JY, Wei Y, Abbruzzese JL, Hortobagyi GN, Hung MC (2007) 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 67:9066–9076. https://doi.org/10.1158/0008-5472.CAN-07-0575
doi: 10.1158/0008-5472.CAN-07-0575
pubmed: 17909010
pmcid: 2570961
Min H, Wei-hong Z (2009) Constitutive activation of signal transducer and activator of transcription 3 in epithelial ovarian carcinoma. J Obstet Gynaecol Res 35:918–925. https://doi.org/10.1111/j.1447-0756.2009.01045.x
doi: 10.1111/j.1447-0756.2009.01045.x
pubmed: 20149042
Morello V, Cabodi S, Sigismund S, Camacho-Leal MP, Repetto D, Volante M, Papotti M, Turco E, Defilippi P (2011) beta1 integrin controls EGFR signaling and tumorigenic properties of lung cancer cells. Oncogene 30:4087–4096. https://doi.org/10.1038/onc.2011.107
doi: 10.1038/onc.2011.107
pubmed: 21478906
Mukhopadhyay UK, Mooney P, Jia L, Eves R, Raptis L, Mak AS (2010) Doubles game: Src-STAT3 versus p53-PTEN in cellular migration and invasion. Mol Cell Biol 30:4980–4995. https://doi.org/10.1128/MCB.00004-10
doi: 10.1128/MCB.00004-10
pubmed: 20733006
pmcid: 2953057
Muller PA, Trinidad AG, Caswell PT, Norman JC, Vousden KH (2014) Mutant p53 regulates dicer through p63-dependent and -independent mechanisms to promote an invasive phenotype. J Biol Chem 289:122–132. https://doi.org/10.1074/jbc.M113.502138
doi: 10.1074/jbc.M113.502138
pubmed: 24220032
Nakagawa T, Iida S, Osanai T, Uetake H, Aruga T, Toriya Y, Takagi Y, Kawachi H, Sugihara K (2008) Decreased expression of SOCS-3 mRNA in breast cancer with lymph node metastasis. Oncol Rep 19:33–39. https://doi.org/10.3892/or.19.1.33
doi: 10.3892/or.19.1.33
pubmed: 18097573
Pan CM, Wang ML, Chiou SH, Chen HY, Wu CW (2016) Oncostatin M suppresses metastasis of lung adenocarcinoma by inhibiting SLUG expression through coordination of STATs and PIASs signalings. Oncotarget 7:60395–60406. https://doi.org/10.18632/oncotarget.10939
doi: 10.18632/oncotarget.10939
pubmed: 27486982
pmcid: 5312391
Park SY, Jeong KJ, Panupinthu N, Yu S, Lee J, Han JW, Kim JM, Lee JS, Kang J, Park CG, Mills GB, Lee HY (2011) Lysophosphatidic acid augments human hepatocellular carcinoma cell invasion through LPA1 receptor and MMP-9 expression. Oncogene 30:1351–1359. https://doi.org/10.1038/onc.2010.517
doi: 10.1038/onc.2010.517
pubmed: 21102517
Pires BR, Mencalha AL, Ferreira GM, de Souza WF, Morgado-Diaz JA, Maia AM, Correa S, Abdelhay ES (2017) NF-kappaB is involved in the regulation of EMT genes in breast cancer cells. PLoS ONE 12:e0169622. https://doi.org/10.1371/journal.pone.0169622
doi: 10.1371/journal.pone.0169622
pubmed: 28107418
pmcid: 5249109
Qiu Z, Huang C, Sun J, Qiu W, Zhang J, Li H, Jiang T, Huang K, Cao J (2007) RNA interference-mediated signal transducers and activators of transcription 3 gene silencing inhibits invasion and metastasis of human pancreatic cancer cells. Cancer Sci 98:1099–1106. https://doi.org/10.1111/j.1349-7006.2007.00485.x
doi: 10.1111/j.1349-7006.2007.00485.x
pubmed: 17459060
Seo JH, Jeong KJ, Oh WJ, Sul HJ, Sohn JS, Kim YK, Cho DY, Kang JK, Park CG, Lee HY (2010) Lysophosphatidic acid induces STAT3 phosphorylation and ovarian cancer cell motility: their inhibition by curcumin. Cancer Lett 288:50–56. https://doi.org/10.1016/j.canlet.2009.06.023
doi: 10.1016/j.canlet.2009.06.023
pubmed: 19647363
Shields MA, Krantz SB, Bentrem DJ, Dangi-Garimella S, Munshi HG (2012) Interplay between beta1-integrin and Rho signaling regulates differential scattering and motility of pancreatic cancer cells by snail and slug proteins. J Biol Chem 287:6218–6229. https://doi.org/10.1074/jbc.M111.308940
doi: 10.1074/jbc.M111.308940
pubmed: 22232555
pmcid: 3307329
Song DG, Kim E, Lee JW (2020) Metastatic behavior analyses of tetraspanin TM4SF5-expressing spheres in three-dimensional (3D) cell culture environment. Arch Pharm Res 43:1162–1172. https://doi.org/10.1007/s12272-020-01291-6
doi: 10.1007/s12272-020-01291-6
pubmed: 33222072
Srivastava J, DiGiovanni J (2016) Non-canonical STAT3 signaling in cancer. Mol Carcinog 55:1889–1898. https://doi.org/10.1002/mc.22438
doi: 10.1002/mc.22438
pubmed: 26649644
Storci G, Sansone P, Mari S, D’Uva G, Tavolari S, Guarnieri T, Taffurelli M, Ceccarelli C, Santini D, Chieco P, Marcu KB, Bonafe M (2010) TNFalpha up-regulates SLUG via the NF-kappaB/HIF1alpha axis, which imparts breast cancer cells with a stem cell-like phenotype. J Cell Physiol 225:682–691. https://doi.org/10.1002/jcp.22264
doi: 10.1002/jcp.22264
pubmed: 20509143
pmcid: 2939957
Welch-Reardon KM, Ehsan SM, Wang K, Wu N, Newman AC, Romero-Lopez M, Fong AH, George SC, Edwards RA, Hughes CC (2014) Angiogenic sprouting is regulated by endothelial cell expression of slug. J Cell Sci 127:2017–2028. https://doi.org/10.1242/jcs.143420
doi: 10.1242/jcs.143420
pubmed: 24554431
pmcid: 4004976
Wheeler SE, Suzuki S, Thomas SM, Sen M, Leeman-Neill RJ, Chiosea SI, Kuan CT, Bigner DD, Gooding WE, Lai SY, Grandis JR (2010) Epidermal growth factor receptor variant III mediates head and neck cancer cell invasion via STAT3 activation. Oncogene 29:5135–5145. https://doi.org/10.1038/onc.2009.279
doi: 10.1038/onc.2009.279
pubmed: 20622897
Xiang M, Huang Y, Dai C, Zou G (2021) MiR-340 regulates the growth and metabolism of renal cell carcinoma cells by targeting frizzled class receptor 3. Arch Pharm Res 44:219–229. https://doi.org/10.1007/s12272-021-01310-0
doi: 10.1007/s12272-021-01310-0
pubmed: 33609235
Yao C, Su L, Shan J, Zhu C, Liu L, Liu C, Xu Y, Yang Z, Bian X, Shao J, Li J, Lai M, Shen J, Qian C (2016) IGF/STAT3/NANOG/Slug signaling axis simultaneously controls epithelial-mesenchymal transition and stemness maintenance in colorectal cancer. Stem Cells 34:820–831. https://doi.org/10.1002/stem.2320
doi: 10.1002/stem.2320
pubmed: 26840943
Zhang J, Liu X, Datta A, Govindarajan K, Tam WL, Han J, George J, Wong C, Ramnarayanan K, Phua TY, Leong WY, Chan YS, Palanisamy N, Liu ET, Karuturi KM, Lim B, Miller LD (2009) RCP is a human breast cancer-promoting gene with Ras-activating function. J Clin Invest 119:2171–2183. https://doi.org/10.1172/JCI37622
doi: 10.1172/JCI37622
pubmed: 19620787
pmcid: 2719918
Zhang S, Wang C, Ma B, Xu M, Xu S, Liu J, Tian Y, Fu Y, Luo Y (2020) Mutant p53 drives cancer metastasis via RCP-mediated Hsp90alpha secretion. Cell Rep 32:107879. https://doi.org/10.1016/j.celrep.2020.107879
doi: 10.1016/j.celrep.2020.107879
pubmed: 32640214
Zhao J, Wu J, Qin Y, Zhang W, Huang G, Qin L (2020) LncRNA PVT1 induces aggressive vasculogenic mimicry formation through activating the STAT3/Slug axis and epithelial-to-mesenchymal transition in gastric cancer. Cell Oncol (dordr) 43:863–876. https://doi.org/10.1007/s13402-020-00532-6
doi: 10.1007/s13402-020-00532-6
Zulkifli AA, Tan FH, Putoczki TL, Stylli SS, Luwor RB (2017) STAT3 signaling mediates tumour resistance to EGFR targeted therapeutics. Mol Cell Endocrinol 451:15–23. https://doi.org/10.1016/j.mce.2017.01.010
doi: 10.1016/j.mce.2017.01.010
pubmed: 28088467