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BMC Cancer
Published in: BMC Cancer 1/2024

Open Access 01-12-2024 | Endometrial Cancer | Research

DOCK1 regulates the malignant biological behavior of endometrial cancer through c-Raf/ERK pathway

Authors: Shangdan Xie, Yanshan Jin, Jiakun Wang, Jingwei Li, Mengjia Peng, Xueqiong Zhu

Published in: BMC Cancer | Issue 1/2024

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Abstract

Background

The effect of DOCK1 gene on the biological behavior of endometrial carcinoma cells and its related pathway has not been reported.

Methods

The immunohistochemical method and western blot were utilized to analyze DOCK1 protein expression in endometrial tissues and cells, respectively. CCK-8, BrdU, transwell and flow cytometry were performed to analyze the effect of DOCK1 expression changes on the viability, proliferation, invasion, migration and apoptosis of endometrial cancer cells, respectively. The effects of DOCK1 gene on Bcl-2, MMP9, Ezrin, E-cadherin and c-RAF/ERK1/2 signaling pathway were evaluated by western blot. The xenograft models were constructed to analyze the effect of DOCK1 in vivo.

Results

DOCK1 expression was increased in endometrial cancer tissues and cells compared with those in normal adjacent tissues and cells. DOCK1 knockout could inhibit the malignant biological behavior of endometrial cancer cells, while DOCK1 overexpression played the opposite effect. The expression of E-cadherin was upregulated and those of MMP9, Ezrin, Bcl-2, p-c-RAF (S338) and p-ERK1/2 (T202/Y204) were downregulated after DOCK1 knockout, while DOCK1 overexpression played the opposite effect. Additionally, Raf inhibitor LY3009120 reversed the function of DOCK1 on malignant biological behavior. In vivo experiment results showed that the growth and weight of transplanted tumors in nude mice were inhibited after DOCK1 knockout. The changes of E-cadherin, MMP9, Ezrin and Bcl-2 expressions in the transplanted tumors were consistent with those in vitro.

Conclusion

DOCK1 could enhance the malignant biological behavior of endometrial cancer cells, which might be through c-RAF/ERK1/2 signaling pathways in vitro and in vivo.
Appendix
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Literature
1.
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer statistics 2020: GLOBOCAN estimates of incidence and Mortality Worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.CrossRefPubMed
2.
3.
Winterhoff B, Thomaier L, Mullany S, Powell MA. Molecular characterization of endometrial cancer and therapeutic implications. Curr Opin Obstet Gynecol. 2020;32(1):76–83.CrossRefPubMed
4.
5.
Crosbie EJ, Kitson SJ, McAlpine JN, Mukhopadhyay A, Powell ME, Singh N. Endometrial cancer. Lancet. 2022;399(10333):1412–28.CrossRefPubMed
6.
7.
8.
Mohan JJ, Narayan P, Padmanabhan RA, Joseph S, Kumar PG, Laloraya M. Silencing of dedicator of cytokinesis (DOCK180) obliterates pregnancy by interfering with decidualization due to blockage of nuclear entry of autoimmune regulator (AIRE). Am J Reprod Immunol. 2018;80(1):e12844.CrossRefPubMed
9.
Grimsley CM, Kinchen JM, Tosello-Trampont AC, Brugnera E, Haney LB, Lu M, et al. Dock180 and ELMO1 proteins cooperate to promote evolutionarily conserved rac-dependent cell migration. J Biol Chem. 2004;279(7):6087–97.CrossRefPubMed
10.
Sanders MA, Ampasala D, Basson MD. DOCK5 and DOCK1 regulate Caco-2 intestinal epithelial cell spreading and migration on collagen IV. J Biol Chem. 2009;284(1):27–35.CrossRefPubMedPubMedCentral
11.
Bagci H, Laurin M, Huber J, Muller WJ, Cote JF. Impaired cell death and mammary gland involution in the absence of Dock1 and Rac1 signaling. Cell Death Dis. 2014;5:e1375.CrossRefPubMedPubMedCentral
12.
Chen DJ, Chen W, Jiang H, Yang H, Wang YC, Chen JH. Downregulation of DOCK1 sensitizes bladder cancer cells to cisplatin through preventing epithelial-mesenchymal transition. Drug Des Devel Ther. 2016;10:2845–53.CrossRefPubMedPubMedCentral
13.
Misek SA, Chen J, Schroeder L, Rattanasinchai C, Sample A, Sarkaria JN, et al. EGFR signals through a DOCK180-MLK3 Axis to drive Glioblastoma Cell Invasion. Mol Cancer Res. 2017;15(8):1085–95.CrossRefPubMed
14.
Wang J, Dai JM, Che YL, Gao YM, Peng HJ, Liu B, et al. Elmo1 helps dock180 to regulate Rac1 activity and cell migration of ovarian cancer. Int J Gynecol Cancer. 2014;24(5):844–50.CrossRefPubMed
15.
Xu Y, Chen X, Pan S, Wang ZW, Zhu X. TM7SF2 regulates cell proliferation and apoptosis by activation of C-Raf/ERK pathway in cervical cancer. Cell Death Discov. 2021;7(1):299.CrossRefPubMedPubMedCentral
16.
Xu W, Xie S, Chen X, Pan S, Qian H, Zhu X. Effects of Quercetin on the efficacy of various chemotherapeutic drugs in Cervical Cancer cells. Drug Des Devel Ther. 2021;15:577–88.CrossRefPubMedPubMedCentral
17.
Zhao F, Siu MK, Jiang L, Tam KF, Ngan HY, Le XF, et al. Overexpression of dedicator of cytokinesis I (Dock180) in ovarian cancer correlated with aggressive phenotype and poor patient survival. Histopathology. 2011;59(6):1163–72.CrossRefPubMed
18.
Zhang B, Li H, Yin C, Sun X, Zheng S, Zhang C, et al. Dock1 promotes the mesenchymal transition of glioma and is modulated by MiR-31. Neuropathol Appl Neurobiol. 2017;43(5):419–32.CrossRefPubMed
19.
Chiang SK, Chang WC, Chen SE, Chang LC. DOCK1 regulates growth and motility through the RRP1B-Claudin-1 pathway in claudin-low breast Cancer cells. Cancers (Basel). 2019;11(11):1762.CrossRefPubMed
20.
Aznavoorian S, Murphy AN, Stetler-Stevenson WG, Liotta LA. Molecular aspects of tumor cell invasion and metastasis. Cancer. 1993;71(4):1368–83.CrossRefPubMed
21.
Barrett A, Pellet-Many C, Zachary IC, Evans IM, Frankel P. p130Cas: a key signalling node in health and disease. Cell Signal. 2013;25(4):766–77.CrossRefPubMed
22.
Feng H, Li Y, Yin Y, Zhang W, Hou Y, Zhang L, et al. Protein kinase A-dependent phosphorylation of Dock180 at serine residue 1250 is important for glioma growth and invasion stimulated by platelet derived-growth factor receptor alpha. Neuro Oncol. 2015;17(6):832–42.CrossRefPubMed
23.
Mondal S, Adhikari N, Banerjee S, Amin SA, Jha T. Matrix metalloproteinase-9 (MMP-9) and its inhibitors in cancer: a minireview. Eur J Med Chem. 2020;194:112260.CrossRefPubMed
24.
Song Y, Ma X, Zhang M, Wang M, Wang G, Ye Y, et al. Ezrin mediates Invasion and Metastasis in Tumorigenesis: a review. Front Cell Dev Biol. 2020;8:588801.CrossRefPubMedPubMedCentral
25.
Kocher HM, Sandle J, Mirza TA, Li NF, Hart IR. Ezrin interacts with cortactin to form podosomal rosettes in pancreatic cancer cells. Gut. 2009;58(2):271–84.CrossRefPubMed
26.
Fang C, Kang Y, E-Cadherin. Context-dependent functions of a quintessential epithelial marker in Metastasis. Cancer Res. 2021;81(23):5800–2.CrossRefPubMed
27.
Riegel K, Schloder J, Sobczak M, Jonuleit H, Thiede B, Schild H, et al. RAF kinases are stabilized and required for dendritic cell differentiation and function. Cell Death Differ. 2020;27(4):1300–15.CrossRefPubMed
28.
29.
Yeh LT, Lin CW, Lu KH, Hsieh YH, Yeh CB, Yang SF, et al. Niclosamide suppresses Migration and Invasion of Human Osteosarcoma cells by repressing TGFBI expression via the ERK Signaling Pathway. Int J Mol Sci. 2022;23(1):484.CrossRefPubMedPubMedCentral
30.
Li B, Xiao Q, Shan L, Song Y. NCAPH promotes cell proliferation and inhibits cell apoptosis of bladder cancer cells through MEK/ERK signaling pathway. Cell Cycle. 2022;21(4):427–38.CrossRefPubMedPubMedCentral
31.
Feng HZ, Hu B, Liu KW, Li YX, Lu XH, Cheng T, et al. Activation of Rac1 by src-dependent phosphorylation of Dock180(Y1811) mediates PDGFRα-stimulated glioma tumorigenesis in mice and humans. J Clin Invest. 2011;121(12):4670–84.CrossRefPubMedPubMedCentral
32.
Ebi H, Costa C, Faber AC, Nishtala M, Kotani H, Juric D, et al. PI3K regulates MEK/ERK signaling in breast cancer via the Rac-GEF, P-Rex1. Proc Natl Acad Sci. 2013;110(52):21124–29.CrossRefPubMedPubMedCentralADS
Metadata
Title
DOCK1 regulates the malignant biological behavior of endometrial cancer through c-Raf/ERK pathway
Authors
Shangdan Xie
Yanshan Jin
Jiakun Wang
Jingwei Li
Mengjia Peng
Xueqiong Zhu
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-024-12030-1

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