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Cited by 77Protein Kinase Regulation and GTPase SignalingMechanisms of cancer metastasisCancer Cells and Metastasis

The WASF3–NCKAP1–CYFIP1 Complex Is Essential for Breast Cancer Metastasis

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Teng, Yong, Qin, Haiyan, Bahassan, Abdulaziz, Bendzunas, N. George, Kennedy, Eileen J., Cowell, John K.·2016·Cancer Research
DOI 10.1158/0008-5472.can-16-0562PMC PMC5010469

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Abstract

Inactivation of the WASF3 gene suppresses invasion and metastasis of breast cancer cells. WASF3 function is regulated through a protein complex that includes the NCKAP1 and CYFIP1 proteins. Here, we report that silencing NCKAP1 destabilizes the WASF3 complex, resulting in a suppression of the invasive capacity of breast, prostate, and colon cancer cells. In an in vivo model of spontaneous metastasis in immunocompromized mice, loss of NCKAP1 also suppresses metastasis. Activation of the WASF protein complex occurs through interaction with RAC1, and inactivation of NCKAP1 prevents the association of RAC1 with the WASF3 complex. Thus, WASF3 depends on NCKAP1 to promote invasion and metastasis. Here, we show that stapled peptides targeting the interface between NCKAP1 and CYFIP1 destabilize the WASF3 complex and suppress RAC1 binding, thereby suppressing invasion. Using a complex-disrupting compound identified in this study termed WANT3, our results offer a mechanistic proof of concept to target this interaction as a novel approach to inhibit breast cancer metastasis. Cancer Res; 76(17); 5133–42. ©2016 AACR.

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  • The HEM2-containing WRC is associated with tumor progression and metastasis in melanoma, non-small cell lung cancer, and breast cancer.

    “the HEM2-containing WRC has been broadly implicated in non-immunological diseases and is especially associated with tumor progression and metastasis in melanoma, non-small cell lung cancer, and breast cancer [46–48].”

    From HEM1 Actin Immunodysregulatory Disorder: Genotypes, Phenotypes, and Future Directions (2022) · cites this paper as [48]

    The Results section (“Knockdown of NCKAP1 suppresses metastasis in breast cancer cells in vivo”; page unavailable) reports reduced metastasis after NCKAP1 knockdown in a breast-cancer mouse model. The Introduction links WASF3 expression to poor prognosis in non-small cell lung cancer, but does not establish that finding for the HEM2/NCKAP1-containing complex; the paper does not address melanoma. Thus it supports the breast-cancer part, not the claimed association across all three cancers. (LLM, conf=0.87)

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Sorted by citations

Authors
Teng, Y., Qin, H., Bahassan, A., Bendzunas, N. G., Kennedy, E. J., & Cowell, J. K.
Affiliations
  • Augusta University (US)
  • University of Georgia (US)
Corresponding author
  • Teng, Yong
  • Kennedy, Eileen J.
ORCID
Venue
Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2016-08-31
Volume
76
Issue
17
Pages
5133-5142
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
DOI
10.1158/0008-5472.can-16-0562
PMC
PMC5010469
OpenAlex
W2485209330
Cited by
77
References
2
Citations by year
2026: 5 · 2025: 3 · 2024: 11 · 2023: 9 · 2022: 10 · 2021: 11 · 2020: 5 · 2019: 14 · 2018: 2 · 2017: 7
FWCI
3.27
Type
journal article
Language
en
Open access
Locations
  • Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (CA120510, CA188439)
  • Department of Defense (W81XWH-14-1-0412)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
WASF3, NCKAP1, CYFIP1, breast cancer metastasis, tumor invasion, Rac1, stapled peptides, anti-metastatic agents, prostate cancer, colon cancer, immunocompromised mouse model
MeSH terms
Animals, Breast Neoplasms, Female, Humans, Neoplasm Invasiveness, Blotting, Western, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, Wiskott-Aldrich Syndrome Protein Family, Mice, Kaplan-Meier Estimate, Gene Knockdown Techniques, Heterografts

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