YWHAZ interacts with DAAM1 to promote cell migration in breast cancer

Abstract

Dishevelled-associated activator of morphogenesis 1 (DAAM1) is a critical driver in facilitating metastasis in breast cancer (BrCa). However, molecular mechanisms for the regulation of DAAM1 activation are only partially elucidated. In this research, the expression levels of YWHAZ and DAAM1 were examined by immunohistochemistry (IHC) staining in BrCa tissues. The functional roles of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ)–DAAM1 axis and their regulator microRNA-613 (miR-613) in BrCa cells and associated molecular mechanisms were demonstrated in vitro. As results, the expression levels of DAAM1 and YWHAZ were significantly upregulated in BrCa tissues compared with normal tissues and remarkably associated with poor prognosis. Besides, DAAM1 and YWHAZ were positively correlated with each other in BrCa tissues. YWHAZ interacted and colocalized with DAAM1 in BrCa cells, which was essential for DAAM1-mediated microfilament remodeling and RhoA activation. Moreover, miR-613 directly targeted both YWHAZ and DAAM1, contributing to inhibiting BrCa cells migration via blocking the complex of YWHAZ–DAAM1. To sum up, these data reveal that YWHAZ regulates DAAM1 activation, and the YWHAZ–DAAM1 complex is directly targeted by the shared post-transcriptional regulator miR-613.

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HLA class II molecule HLA-DRA identifies immuno-hot tumors and predicts the therapeutic response to anti-PD-1 immunotherapy in NSCLC

“…Staining was visualized with DAB and hematoxylin counterstain, and stained sections were captured using Aperio Digital Pathology Slide Scanners. For semi-quantitative analysis, the stained sections were independently evaluated by two pathologists according to the evaluation standard on a 12-point scale by calculating the immunoreactivity score (IRS) [ 32 ].…”

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“…The stained sections were independently evaluated by two pathologists. Expression levels of CDCP1 and EGFR in tumor cells were semiquantitatively assessed by estimating the immunoreactivity score (IRS) [ 19 ]. Briefly, the percentage of positively stained cells was scored as 0–4: 0 (< 5%), 1 (6–25%), 2 (26–50%), 3 (51–75%) and 4 (> 75%).…”