Reference Detail

Ref Type Journal Article
PMID (27432794)
Authors Teng Y, Qin H, Bahassan A, Bendzunas NG, Kennedy EJ, Cowell JK
Title The WASF3-NCKAP1-CYFIP1 Complex Is Essential for Breast Cancer Metastasis.
Journal Cancer research
Vol 76
Issue 17
Date 2016 Sep 01
URL
Abstract Text 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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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
WANT3 WANT3 3 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
WANT3 WANT3 is a peptide that targets NCKAP1 thereby disrupting the interaction between NCKAP1 and WASF3, and may result in suppression of cell invasion (PMID: 27432794).
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown prostate cancer not applicable WANT3 Preclinical - Cell culture Actionable In a preclinical study, WANT3 treatment resulted in suppression of cell invasion of prostate cancer cells in culture (PMID: 27432794). 27432794
Unknown unknown breast cancer not applicable WANT3 Preclinical - Cell culture Actionable In a preclinical study, WANT3 treatment resulted in suppression of cell invasion of breast cancer cells in culture (PMID: 27432794). 27432794
Unknown unknown colon cancer not applicable WANT3 Preclinical - Cell culture Actionable In a preclinical study, WANT3 treatment resulted in suppression of cell invasion of colon cancer cells in culture (PMID: 27432794). 27432794