AI Article Synopsis
- Triple-negative breast cancer (TNBC) is highly aggressive with poor outcomes, highlighting the urgent need for new treatment approaches targeting specific pathways.
- N-α-acetyltransferase 20 (NAA20) is overexpressed in TNBC tissues and its knockdown reduces cell viability, migration, and invasion, as well as affecting EGFR signaling pathways.
- The study also indicates that NAA20 interacts with Rab5A, which plays a role in activating EGFR signaling; its knockdown in TNBC cells leads to reduced tumor growth in xenograft models, suggesting NAA20 as a potential therapeutic target.
Article Abstract
Triple-negative breast cancer (TNBC) is the most aggressive subtype with poor prognosis and high mortality. To improve the prognosis and survival of TNBC patients, it is necessary to explore new targets and signaling pathways to develop novel therapies for TNBC treatment. N-α-acetyltransferase 20 (NAA20) is one of the catalytic subunits of N-terminal acetyltransferase (NatB). It has been reported that NAA20 played a critical role in cancer progression. In this study, we found that NAA20 expression was markedly higher in TNBC tissues than in paracancerous normal tissues using The Cancer Genome Atlas (TCGA) analysis. This result was further confirmed by qRT-PCR and immunohistochemistry (IHC). Knockdown of NAA20 significantly inhibited TNBC cell viability by CCK8 and colony formation assays and cell migration and invasion by Transwell assays. Additionally, NAA20 knockdown decreased the expression of EGFR in TNBC cells. Upon stimulation with EGF and knockdown of NAA20, EGFR internalization and degradation were observed by confocal microscopy. The western blot results showed that NAA20 knockdown down-regulated PI3K, AKT, and mTOR phosphorylation. Next, we further explored the underlying molecular mechanisms of NAA20 by co-immunoprecipitation (Co-IP). The results suggested that there was an interacting relationship between NAA20 and Rab5A. Over-expression of NAA20 could potentiate the expression of Rab5A. Furthermore, the knockdown of Rab5A inhibited EGFR expression and the phosphorylation of downstream signaling targets. NAA20 over-expression offset the knockdown effect of Rab5A and activated EGFR signaling. Finally, we constructed a xenograft mouse model transfected TNBC cells to investigate the role of NAA20 in vivo. NAA20 knockdown markedly suppressed tumor growth and decreased tumor volume and weight. In conclusion, our study demonstrated that NAA20, a novel target of TNBC, could promote TNBC progression by regulating Rab5A-mediated activation of EGFR signaling.
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| http://dx.doi.org/10.1016/j.cellsig.2023.110922 | DOI Listing |
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Article Synopsis
- Triple-negative breast cancer (TNBC) is highly aggressive with poor outcomes, highlighting the urgent need for new treatment approaches targeting specific pathways.
- N-α-acetyltransferase 20 (NAA20) is overexpressed in TNBC tissues and its knockdown reduces cell viability, migration, and invasion, as well as affecting EGFR signaling pathways.
- The study also indicates that NAA20 interacts with Rab5A, which plays a role in activating EGFR signaling; its knockdown in TNBC cells leads to reduced tumor growth in xenograft models, suggesting NAA20 as a potential therapeutic target.
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