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Cited by 87Mechanisms of cancer metastasisCellular Mechanics and InteractionsProtein Kinase Regulation and GTPase Signaling

Cyfip1 is a putative invasion suppressor in epithelial cancers

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Silva, Jose M., Ezhkova, Elena, Silva, Javier, Heart, Stephen, Castillo, Mireia, Campos, Yolanda, Castro, Veronica, Bonilla, Felix +5 more·2009·Cell
DOI 10.1016/j.cell.2009.04.013PMC PMC2754270
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Abstract

Identification of bona fide tumor suppressors is often challenging because of the large number of genetic alterations present in most human cancers. To evaluate candidate genes present within chromosomal regions recurrently deleted in human cancers, we coupled high-resolution genomic analysis with a two-stage genetic study using RNA interference (RNAi). We found that Cyfip1, a subunit of the WAVE complex, which regulates cytoskeletal dynamics, is commonly deleted in human epithelial cancers. Reduced expression of CYFIP1 is commonly observed during invasion of epithelial tumors and is associated with poor prognosis in this setting. Silencing of Cyfip1 disturbed normal epithelial morphogenesis in vitro and cooperated with oncogenic Ras to produce invasive carcinomas in vivo. Mechanistically, we have linked alterations in WAVE-regulated actin dynamics with impaired cell-cell adhesion and cell-ECM interactions. Thus, we propose Cyfip1 as an invasion suppressor gene.

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  • Knockdown of CYFIP2 induces a dramatic reduction of proliferation while knockdown of FMR1 does not have an impact on these cells.

    “Conversely, knockdown of CYFIP2 induces a dramatic reduction of proliferation while knockdown of FMR1 does not have an impact on these cells (Silva et al., 2009).”

    From New insights into the regulatory function of CYFIP1 in the context of WAVE- and FMRP-containing complexes (2017) · cites this paper as Silva et al., 2009

    In Results, under “Cyfip1 regulates epithelial morphogenesis as part of the WAVE complex” (page unavailable), the paper reports a dramatic reduction in MCF-10A cell proliferation after Cyfip2 RNAi. It also reports no evident difference in 2D colonies or 3D acinar structures after FMR1 suppression, but does not establish that FMR1 knockdown had no impact on proliferation or on the cells generally. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • This phenotype is also present when WAVE1 or NAP1 are knocked down.

    “This phenotype is also present when WAVE1 or NAP1 are knocked down.”

    From New insights into the regulatory function of CYFIP1 in the context of WAVE- and FMRP-containing complexes (2017) · cites this paper as Silva et al., 2009

    In Results, under “Cyfip1 regulates epithelial morphogenesis as part of the WAVE complex” (page unavailable), the paper reports that knocking down Nckap1 and Wave-2 produced phenotypes similar to Cyfip1 silencing. This supports the Nckap1 knockdown finding, but the paper names Wave-2, not WAVE1, as the component knocked down in that experiment. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Depletion of CYFIP1 in epithelial cancer cells interferes with the morphology of the cells and induces invasion.

    “(iii) depletion of CYFIP1 in epithelial cancer cells interferes with the morphology of the cells and induces invasion (Silva et al., 2009).”

    From New insights into the regulatory function of CYFIP1 in the context of WAVE- and FMRP-containing complexes (2017) · cites this paper as Silva et al., 2009

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Authors
Silva, J. M., Ezhkova, E., Silva, J., Heart, S., Castillo, M., Campos, Y., Castro, V., Bonilla, F., Cordon-Cardo, C., Muthuswamy, S. K., Powers, S., Fuchs, E., & Hannon, G. J.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Hospital Virgen de la Salud (ES)
Corresponding author
Hannon, Gregory J.
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2009-06
Volume
137
Issue
6
Pages
1047-1061
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2009.04.013
PMC
PMC2754270
OpenAlex
W2129158239
Cited by
87
References
2
Citations by year
2026: 4 · 2025: 3 · 2024: 1 · 2023: 8 · 2022: 4 · 2021: 2 · 2020: 6 · 2019: 4 · 2018: 3 · 2017: 5 · 2016: 5 · 2015: 5 · 2014: 7 · 2013: 5 · 2012: 8
FWCI
3.36
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
  • RUIdeRA - Institutional University Repository (University of Castilla-La Mancha) (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • U.S. Public Health Service (K99/R00 54010101-5411)
  • National Cancer Institute (P01CA013106)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR027883, R01 AR27883)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
CYFIP1, tumor suppressor, WAVE complex, actin cytoskeleton dynamics, cell-cell adhesion, cell-matrix interactions, oncogenic Ras, tumor suppressor loss, epithelial morphogenesis, prognosis
MeSH terms
Animals, Carcinoma, Cells, Cultured, Epithelial Cells, Humans, Neoplasm Invasiveness, Neoplasm Transplantation, Transplantation, Heterologous, Keratinocytes, Gene Expression Regulation, Neoplastic, Gene Expression Profiling, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, Mice

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