Rho A Regulates Epidermal Growth Factor-Induced Human Osteosarcoma MG63 Cell Migration

International Journal of Molecular Sciences
Jinyang WangWenhua Huang

Abstract

Osteosarcoma, the most common primary bone tumor, occurs most frequently in children and adolescents and has a 5-year survival rate, which is unsatisfactory. As epidermal growth factor receptor (EGFR) positively correlates with TNM (tumor-node-metastasis) stage in osteosarcoma, EGFR may play an important role in its progression. The purpose of this study was to explore potential mechanisms underlying this correlation. We found that EGF promotes MG63 cell migration and invasion as well as stress fiber formation via Rho A activation and that these effects can be reversed by inhibiting Rho A expression. In addition, molecules downstream of Rho A, including ROCK1, LIMK2, and Cofilin, are activated by EGF in MG63 cells, leading to actin stress fiber formation and cell migration. Moreover, inhibition of ROCK1, LIMK2, or Cofilin in MG63 cells using known inhibitors or short hairpin RNA (shRNA) prevents actin stress fiber formation and cell migration. Thus, we conclude that Rho A/ROCK1/LIMK2/Cofilin signaling mediates actin microfilament formation in MG63 cells upon EGFR activation. This novel pathway provides a promising target for preventing osteosarcoma progression and for treating this cancer.

References

Aug 1, 1995·Biochemical Society Transactions·C D Nobes, A Hall
Oct 13, 2001·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Y Yarden
May 14, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Leo KagerUNKNOWN Cooperative German-Austrian-Swiss Osteosarcoma Study Group
Jul 16, 2004·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Yoh DobashiAkishi Ooi
Jul 22, 2004·The Oncologist·Neyssa MarinaRichard Gorlick
Sep 7, 2004·The International Journal of Developmental Biology·Jury M Vasiliev
Dec 14, 2004·Biochimica Et Biophysica Acta·Salvador A BenitahJuan Carlos Lacal
Dec 26, 2006·The International Journal of Biochemistry & Cell Biology·Ora Bernard
Mar 22, 2007·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Xosé R BusteloInmaculada M Berenjeno
May 19, 2007·Human Pathology·Yong Hannah WenM Alba Greco
Jan 23, 2009·Cancer Metastasis Reviews·Shuh NarumiyaToshimasa Ishizaki
Sep 9, 2010·Cell Communication and Signaling : CCS·Matteo Parri, Paola Chiarugi
Nov 16, 2010·Current Opinion in Nephrology and Hypertension·Radko Komers
Nov 18, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jens H W PahlArjan C Lankester
Nov 4, 2015·Journal of Experimental & Clinical Cancer Research : CR·Florian SeveldaWalter Berger

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Citations

Jun 20, 2019·American Journal of Physiology. Cell Physiology·Deng-Fu Guo, Kamal Rahmouni
Jun 18, 2020·Journal of Cell Science·Tejeshwar C RaoAlexa L Mattheyses
Oct 28, 2020·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Sho YokoyamaMasaaki Takechi
Aug 8, 2021·International Journal of Molecular Sciences·Nadezhda BarvitenkoAntonella Pantaleo

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Methods Mentioned

BETA
GTPase
GTPases
pull-down
PCR
Transfection
transfections
Fluorescence
Protein Assay
electrophoresis

Software Mentioned

ZEN
ImageJ
SPSS

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