ADP-ribosylation factor 1 expression regulates epithelial-mesenchymal transition and predicts poor clinical outcome in triple-negative breast cancer

Oncotarget
Sabrina SchliengerAudrey Claing

Abstract

Metastatic capacities are fundamental features of tumor malignancy. ADP-ribosylation factor (ARF) 1 has emerged as a key regulator of invasion in breast cancer cells. However, the importance of this GTPase, in vivo, remains to be demonstrated. We report that ARF1 is highly expressed in breast tumors of the most aggressive and advanced subtypes. Furthermore, we show that lowered expression of ARF1 impairs growth of primary tumors and inhibits lung metastasis in a murine xenograft model. To understand how ARF1 contributes to invasiveness, we used a poorly invasive breast cancer cell line, MCF7 (ER+), and examined the effects of overexpressing ARF1 to levels similar to that found in invasive cell lines. We demonstrate that ARF1 overexpression leads to the epithelial-mesenchymal transition (EMT). Mechanistically, ARF1 controls cell-cell adhesion through ß-catenin and E-cadherin, oncogenic Ras activation and expression of EMT inducers. We further show that ARF1 overexpression enhances invasion, proliferation and resistance to a chemotherapeutic agent. In vivo, ARF1 overexpressing MCF7 cells are able to form more metastases to the lung. Overall, our findings demonstrate that ARF1 is a molecular switch for cancer progression and thus ...Continue Reading

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Citations

Jan 7, 2017·Biochemical and Biophysical Research Communications·Qihui WuGang Yin
Dec 23, 2016·The Journal of Cell Biology·Elisabeth Genot
Sep 3, 2016·Small GTPases·Cristina CasalouDuarte C Barral
Feb 26, 2020·International Journal of Molecular Sciences·Amaia Navarro-CorcueraMaría J Iraburu
Dec 3, 2020·British Journal of Cancer·Imran Khan, Patricia S Steeg
Aug 5, 2021·Nature Communications·Jenna GiubilaroStéphane A Laporte

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Methods Mentioned

BETA
GTPases
nucleotide exchange
GTPase
zymography
xenograft
transfection
FACS
immunoprecipitations

Software Mentioned

Icy
FlowJo
ImageQuant
GraphPad
Fiji
Prism

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