ADP-ribosylation factor 1 expression regulates epithelial-mesenchymal transition and predicts poor clinical outcome in triple-negative breast cancer
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// Sabrina Schlienger 1 , Shirley Campbell 1 , Sarah Pasquin 1 , Louis Gaboury 2 and Audrey Claing 1 1 Department of Pharmacology, Faculty of Medicine, Université de Montréal, Montreal, Canada 2 Department of Pathology and Cell Biology, Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, Canada Correspondence to: Audrey Claing, email: // Keywords : ADP-ribosylation factor (ARF), breast cancer, EMT, metastasis, invasion Received : August 28, 2015 Accepted : February 05, 2016 Published : February 18, 2016 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 suggest that limiting the expression/activation of this GTPase could help improve outcome for breast cancer patients.
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ARF6 promotes cellular motility and invasion of glioma and breast cancer cells by inducing internalization of E-cadherin and breakdown of adherence junction.
“ARF6 promotes cellular motility and invasion of glioma and breast cancer cells by inducing internalization of E-cadherin and breakdown of adherence junction [114].”
From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [114]
The Results section (page unavailable) reports increased motility in ARF6-overexpressing breast cancer cells and reduced E-cadherin at their cell-cell junctions. It does not establish E-cadherin internalization as the mechanism, and it does not study glioma cells. Contrary to the invasion claim, ARF6 overexpression had no significant effect in the reported breast-cell invasion assay. (LLM, conf=0.88)
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ARF1 controls proliferation of breast cancer cells by regulating the retinoblastoma protein
Boulay, P.-L., Schlienger, S., Lewis-Saravalli, S., Vitale, N., Ferbeyre, G., & Claing, A. (2011) · Oncogene · doi:10.1038/onc.2011.100 · Cited by 61 · see citing works
Self-citationSchlienger, S., Ramirez, R. A. M., & Claing, A. (2015) · Cellular Signalling · doi:10.1016/j.cellsig.2014.11.032 · Cited by 50 · see citing works
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Insights of Endocytosis Signaling in Health and Disease
Pathak, C., Vaidya, F. U., Waghela, B. N., Jaiswara, P. K., Gupta, V. K., Kumar, A., Rajendran, B. K., & Ranjan, K. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032971 · Cited by 59 · see citing works
- Authors
- Schlienger, S., Campbell, S., Pasquin, S., Gaboury, L., & Claing, A.
- Affiliations
- Université de Montréal (CA)
- Institute for Research in Immunology and Cancer (CA)
- Corresponding author
- Claing, Audrey
- Venue
- Oncotarget
- Publisher
- Impact Journals, LLC
- Published
- 2016-02-18
- Volume
- 7
- Issue
- 13
- Pages
- 15811-15827
- ISSN
- 1949-2553 (ISSN-L)
- PMC
- PMC4941279
- OpenAlex
- W2295585001
- Cited by
- 26
- References
- 2
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 1 · 2020: 4 · 2019: 1 · 2017: 2 · 2016: 3
- FWCI
- 1.08
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Oncotarget (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- Arf1, epithelial-mesenchymal transition, triple-negative breast cancer, lung metastasis, tumor invasion, cell-cell adhesion, β-catenin, E-cadherin, oncogenic Ras, chemoresistance, prognostic factors, GTPase
- MeSH terms
- Animals, Female, Humans, Mice, SCID, ADP-Ribosylation Factor 1, Cell Line, Tumor, Mice, Epithelial-Mesenchymal Transition, Heterografts, Triple Negative Breast Neoplasms
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