CoChat
Sign Up
Cited by 22Protein Kinase Regulation and GTPase SignalingMechanisms of cancer metastasisCancer Cells and Metastasis

Downregulation of Dock1 and Elmo1 suppresses the migration and invasion of triple‑negative breast cancer epithelial cells through the RhoA/Rac1 pathway

Open access
Liang, Yueyang, Wang, Shushu, Zhang, Yi·2018·Oncology Letters
DOI 10.3892/ol.2018.9077PMC PMC6096110
Open this paper in CoChat — free accountOpen PDF

Abstract

Dedicator of cytokinesis 1 (Dock1), a guanine nucleotide exchange factor, has been proven to facilitate cell survival, motility and proliferation via the activation of Ras-related C3 botulinum toxin substrate 1 (Rac1). Engulfment and cell motility 1 (Elmo1) serves as a mammalian homolog of Ced-12, which has been evolutionarily conserved from worm to human. The present study aimed to investigate the roles and mechanisms of Dock1 and Elmo1 in the migration and invasion of triple-negative breast cancer (TNBC) epithelial cells. Cell Counting kit-8, cell migration and cell invasion assays were performed to assess cell viability, migration and invasion, respectively. A plate clone formation assay was performed to determine cell proliferation. Western blot analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assays were used to evaluate mRNA and protein expression. The results revealed that the downregulation of Dock1 and Elmo1 inhibited cell viability, suppressed migration and invasion, and reduced Rac1 activity in MDA-MB-231 cells. Furthermore, downregulation of Dock1 and Elmo1 also attenuated the expression of migration-associated proteins and affected the Ras homolog gene family, member A (RhoA)/Rac1 pathway in MDA-MB-231 cells. In conclusion, the results of the present study suggested that the downregulation of Dock1 and Elmo1 suppresses the migration and invasion of TNBC epithelial cells through the RhoA/Rac1 pathway.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3892/ol.2018.9077

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • DOCK1 has reported roles in cell migration, invasion, and phagocytosis.

    “It has reported roles in cell migration, invasion, and phagocytosis (48, 51, 52, 53, 54).”

    From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [51]

    The Results and Discussion report that reducing Dock1 suppresses migration and invasion in MDA-MB-231 cells. The Introduction mentions phagocytosis of apoptotic cells as a role of Elmo1, not Dock1, so this copy does not establish that part of the claim for Dock1. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 39

  1. [1]DeSantis C Ma J Bryan L Jemal A Breast cancer statistics, 2013 CA Cancer J Clin 64 52 62 2014 10.3322/caac.21203 24114568 · DOI
  2. [2]Donepudi MS Kondapalli K Amos SJ Venkanteshan P Breast cancer statistics and markers J Cancer Res Ther 10 506 511 2014 25313729
  3. [3]Weigelt B Eberle C Cowell CF Ng CK Reis-Filho JS Metaplastic breast carcinoma: More than a special type Nat Rev Cancer 14 147 148 2014 10.1038/nrc3637 25688406 · DOI
  4. [4]Denkert C Liedtke C Tutt A von Minckwitz G Molecular alterations in triple-negative breast cancer-the road to new treatment strategies Lancet 389 2430 2442 2017 10.1016/S0140-6736(16)32454-0 27939063 · DOI
  5. [5]Bianchini G Balko JM Mayer IA Sanders ME Gianni L Triple-negative breast cancer: Challenges and opportunities of a heterogeneous disease Nat Rev Clin Oncol 13 674 690 2016 10.1038/nrclinonc.2016.66 27184417 PMC5461122 · DOI · Paper page
  6. [6]Wojciak-Stothard B Ridley AJ Rho GTPases and the regulation of endothelial permeability Vascul Pharmacol 39 187 199 2002 10.1016/S1537-1891(03)00008-9 12747959 · DOI
  7. [7]Kamai T Yamanishi T Shirataki H Takagi K Asami H Ito Y Yoshida K Overexpression of RhoA, Rac1, and Cdc42 GTPases is associated with progression in testicular cancer Clin Cancer Res 10 4799 4805 2004 10.1158/1078-0432.CCR-0436-03 15269155 · DOI
  8. [8]Rihet S Vielh P Camonis J Goud B Chevillard S de Gunzburg J Mutation status of genes encoding RhoA, Rac1, and Cdc42 GTPases in a panel of invasive human colorectal and breast tumors J Cancer Res Clin Oncol 127 733 738 2001 11768613 PMC12164658
  9. [9]Pan Y Bi F Liu N Xue Y Yao X Zheng Y Fan D Expression of seven main Rho family members in gastric carcinoma Biochem Biophys Res Commun 315 686 691 2004 10.1016/j.bbrc.2004.01.108 14975755 · DOI
  10. [10]Simpson KJ Dugan AS Mercurio AM Functional analysis of the contribution of RhoA and RhoC GTPases to invasive breast carcinoma Cancer Res 64 8694 8701 2004 10.1158/0008-5472.CAN-04-2247 15574779 · DOI
  11. [11]Cote JF Vuori K GEF what? Dock180 and related proteins help Rac to polarize cells in new ways Trends Cell Biol 17 383 393 2007 10.1016/j.tcb.2007.05.001 17765544 PMC2887429 · DOI
  12. [12]Feng H Hu B Liu KW Li Y Lu X Cheng T Yiin JJ Lu S Keezer S Fenton T Activation of Rac1 by Src-dependent phosphorylation of Dock180 (Y1811) mediates PDGFRα-stimulated glioma tumorigenesis in mice and humans J Clin Invest 121 4670 4684 2011 10.1172/JCI58559 22080864 PMC3223070 · DOI
  13. [13]Gumienny TL Brugnera E Tosello-Trampont AC Kinchen JM Haney LB Nishiwaki K Walk SF Nemergut ME Macara IG Francis R CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration Cell 107 27 41 2001 10.1016/S0092-8674(01)00520-7 11595183 · DOI · Paper page
  14. [14]Kim K Lee J Lee SA Moon H Park B Kim D Joo YE Park D Intermolecular steric inhibition of Ephexin4 is relieved by Elmo1 Sci Rep 7 4404 2017 10.1038/s41598-017-04810-6 28667327 PMC5493634 · DOI
  15. [15]Hamoud N Tran V Croteau LP Kania A Cote JF G-protein coupled receptor BAI3 promotes myoblast fusion in vertebrates Proc Natl Acad Sci USA 111 3745 3750 2014 10.1073/pnas.1313886111 24567399 PMC3956190 · DOI
  16. [16]Hochreiter-Hufford AE Lee CS Kinchen JM Sokolowski JD Arandjelovic S Call JA Klibanov AL Yan Z Mandell JW Ravichandran KS Phosphatidylserine receptor BAI1 and apoptotic cells as new promoters of myoblast fusion Nature 497 263 267 2013 10.1038/nature12135 23615608 PMC3773542 · DOI
  17. [17]Katoh H Negishi M RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo Nature 424 461 464 2003 10.1038/nature01817 12879077 · DOI
  18. [18]Park D Ravichandran KS Emerging roles of brain-specific angiogenesis inhibitor 1 Adv Exp Med Biol 706 167 178 2010 10.1007/978-1-4419-7913-1_15 21618836 · DOI
  19. [19]Park D Tosello-Trampont AC Elliott MR Lu M Haney LB Ma Z Klibanov AL Mandell JW Ravichandran KS BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module Nature 450 430 434 2007 10.1038/nature06329 17960134 · DOI
  20. [20]Xiao Y Peng Y Wan J Tang G Chen Y Tang J Ye WC Ip NY Shi L The atypical guanine nucleotide exchange factor Dock4 regulates neurite differentiation through modulation of Rac1 GTPase and actin dynamics J Biol Chem 288 20034 20045 2013 10.1074/jbc.M113.458612 23720743 PMC3707701 · DOI · Paper page
  21. [21]Laurin M Huber J Pelletier A Houalla T Park M Fukui Y Haibe-Kains B Muller WJ Côté JF Rac-specific guanine nucleotide exchange factor DOCK1 is a critical regulator of HER2-mediated breast cancer metastasis Proc Natl Acad Sci USA 110 7434 7439 2013 10.1073/pnas.1213050110 23592719 PMC3645577 · DOI
  22. [22]Livak KJ 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 10.1006/meth.2001.1262 11846609 · DOI · Paper page
  23. [23]Jarzynka MJ Hu B Hui KM Bar-Joseph I Gu W Hirose T Haney LB Ravichandran KS Nishikawa R Cheng SY ELMO1 and Dock180, a bipartite Rac1 guanine nucleotide exchange factor, promote human glioma cell invasion Cancer Res 67 7203 7211 2007 10.1158/0008-5472.CAN-07-0473 17671188 PMC2867339 · DOI
  24. [24]Grimsley CM Kinchen JM Tosello-Trampont AC Brugnera E Haney LB Lu M Chen Q Klingele D Hengartner MO Ravichandran KS Dock180 and ELMO1 proteins cooperate to promote evolutionarily conserved Rac-dependent cell migration J Biol Chem 279 6087 6097 2004 10.1074/jbc.M307087200 14638695 · DOI · Paper page
  25. [25]Wang J Dai JM Che YL Gao YM Peng HJ Liu B Wang H Linghu H Elmo1 helps dock180 to regulate Rac1 activity and cell migration of ovarian cancer Int J Gynecol Cancer 24 844 850 2014 10.1097/IGC.0000000000000137 24819662 · DOI
  26. [26]Balassa T Berta G Jakab L Bohonyi N Szekeres-Bartho J The effect of the Progesterone-Induced Blocking Factor (PIBF) on E-cadherin expression, cell motility and invasion of primary tumour cell lines J Reprod Immunol 125 8 15 2018 10.1016/j.jri.2017.10.047 29107859 · DOI
  27. [27]Sanders MA Ampasala D Basson MD DOCK5 and DOCK1 regulate Caco-2 intestinal epithelial cell spreading and migration on collagen IV J Biol Chem 284 27 35 2009 10.1074/jbc.M808010200 19004829 PMC2610524 · DOI
  28. [28]Shi L Zhang B Sun X Zhang X Lv S Li H Wang X Zhao C Zhang H Xie X CC chemokine ligand 18 (CCL18) promotes migration and invasion of lung cancer cells by binding to Nir1 through Nir1-ELMO1/DOC180 signaling pathway Mol Carcinog 55 2051 2062 2016 10.1002/mc.22450 26756176 · DOI
  29. [29]Tajiri H Uruno T Shirai T Takaya D Matsunaga S Setoyama D Watanabe M Kukimoto-Niino M Oisaki K Ushijima M Targeting ras-driven cancer cell survival and invasion through selective inhibition of DOCK1 Cell Rep 19 969 980 2017 10.1016/j.celrep.2017.04.016 28467910 · DOI
  30. [30]Gu S Papadopoulou N Nasir O Föller M Alevizopoulos K Lang F Stournaras C Activation of membrane androgen receptors in colon cancer inhibits the prosurvival signals Akt/bad in vitro and in vivo and blocks migration via vinculin/actin signaling Mol Med 17 48 58 2011 10.2119/molmed.2010.00120 20957335 PMC3022983 · DOI
  31. [31]Huang C Rajfur Z Yousefi N Chen Z Jacobson K Ginsberg MH Talin phosphorylation by Cdk5 regulates Smurf1-mediated talin head ubiquitylation and cell migration Nat Cell Biol 11 624 630 2009 10.1038/ncb1868 19363486 PMC2714540 · DOI
  32. [32]Sieg DJ Hauck CR Ilic D Klingbeil CK Schaefer E Damsky CH Schlaepfer DD FAK integrates growth-factor and integrin signals to promote cell migration Nat Cell Biol 2 249 256 2000 10.1038/35010517 10806474 · DOI
  33. [33]Dreissigacker U Mueller MS Unger M Siegert P Genze F Gierschik P Giehl K Oncogenic K-Ras down-regulates Rac1 and RhoA activity and enhances migration and invasion of pancreatic carcinoma cells through activation of p38 Cell Signal 18 1156 1168 2006 10.1016/j.cellsig.2005.09.004 16257181 · DOI
  34. [34]Gulhati P Bowen KA Liu J Stevens PD Rychahou PG Chen M Lee EY Weiss HL O'Connor KL Gao T Evers BM mTORC1 and mTORC2 regulate EMT, motility, and metastasis of colorectal cancer via RhoA and Rac1 signaling pathways Cancer Res 71 3246 3256 2011 10.1158/0008-5472.CAN-10-4058 21430067 PMC3085654 · DOI
  35. [35]Parri M Chiarugi P Rac and Rho GTPases in cancer cell motility control Cell Commun Signal 8 23 2010 10.1186/1478-811X-8-23 20822528 PMC2941746 · DOI
  36. [36]Zhao Y Li J Xing Y Wang J Lu C Xin X Geng M N-acetylglucosaminyltransferase V mediates cell migration and invasion of mouse mammary tumor cells 4TO7 via RhoA and Rac1 signaling pathway Mol Cell Biochem 309 199 208 2008 10.1007/s11010-007-9656-6 18060576 · DOI
  37. [37]Baugher PJ Krishnamoorthy L Price JE Dharmawardhane SF Rac1 and Rac3 isoform activation is involved in the invasive and metastatic phenotype of human breast cancer cells Breast Cancer Res 7 R965 R974 2005 10.1186/bcr1329 16280046 PMC1410764 · DOI
  38. [38]Bourguignon LY Zhu H Shao L Chen YW CD44 interaction with tiam1 promotes Rac1 signaling and hyaluronic acid-mediated breast tumor cell migration J Biol Chem 275 1829 1838 2000 10.1074/jbc.275.3.1829 10636882 · DOI
  39. [39]Burbelo P Wellstein A Pestell RG Altered Rho GTPase signaling pathways in breast cancer cells Breast Cancer Res Treat 84 43 48 2004 10.1023/B:BREA.0000018422.02237.f9 14999153 · DOI

Cited by

Sorted by citations

Authors
Liang, Y., Wang, S., & Zhang, Y.
Affiliations
Army Medical University (CN)
Corresponding author
Zhang, Yi
ORCID
Wang, Shushu
Venue
Oncology Letters
Publisher
Spandidos Publications
Published
2018-07-04
Volume
16
Issue
3
Pages
3481-3488
ISSN
  • 1792-1074 (ISSN-L)
  • 1792-1082
DOI
10.3892/ol.2018.9077
PMC
PMC6096110
OpenAlex
W2809758323
Cited by
22
References
0
Citations by year
2025: 3 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 4 · 2020: 5 · 2019: 2
FWCI
0.98
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Oncology Letters (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
DOCK1, ELMO1, triple-negative breast cancer, cell migration, cell invasion, Rac1, guanine nucleotide exchange factor, MDA-MB-231 cells, cell proliferation, epithelial cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review