Journal: The Journal of Biological Chemistry

Article Title: Blockade of a novel MAP4K4-LATS2-SASH1-YAP1 cascade inhibits tumorigenesis and metastasis in luminal breast cancer

doi: 10.1016/j.jbc.2024.107309

Figure Lengend Snippet: SASH1 expression is negatively correlated with MAP4K4 expression in luminal-subtype breast cancer tissues. A , a representative image of IHC staining for SASH1 and MAP4K4 in 30 benign breast tissues. Correlation analysis of the SASH1 and MAP4K4 scores revealed that SASH1 expression was positively correlated with MAP4K4 expression ( right panel ). B , correlation analysis of MAP4K4 and SASH1 expression in 111 normal breast specimens suggested that MAP4K4 expression was significantly associated with SASH1 expression at the transcriptional level. The data were obtained from The Cancer Genome Atlas (TCGA) ( https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga ). C , representative image of IHC staining for SASH1 and MAP4K4 in 119 luminal-subtype breast cancer tissues, namely, 64 luminal A and 55 luminal B tissues. In the luminal subtype tissues, SASH1 expression was significantly negatively associated with MAP4K4 expression. D , a representative image of IHC staining for SASH1 and MAP4K4 in 17 Her2-positive subtype breast cancer tissues. In the Her2-positive subtype tissues, SASH1 expression was not associated with MAP4K4 expression. E , a representative image of IHC staining for SASH1 and MAP4K4 in 14 TNBC subtype breast cancer tissues. In the TNBC subtype tissues, SASH1 expression was not associated with MAP4K4 expression. Magnification of the images in Figure 2 , A – E : 10× ; scale bar: 10 μm. F , correlation analysis of MAP4K4 and SASH1 expression in 1054 breast cancer specimens from the TCGA database revealed that MAP4K4 expression was not associated with SASH1 expression at the transcriptional level. The extent of the correlation between SASH1 and MAP4K4 was identified via bivariate linear correlation analysis in SPSS v.16.0 software. GraphPad Prism v.6.0 software was used to construct the figures. G , decreased expression of SASH1 and increased expression of MAP4K4 were detected in 10 representative luminal-subtype breast cancer tissues compared to the paired paracancerous tissues. N: paracancerous tissues, C: cancer tissues. H , SASH1 downregulation and MAP4K4 upregulation were detected via western blotting in various breast cancer cell lines compared with normal breast cells (MCF10A).

Article Snippet: Human breast cancer tissues, normal breast tissues, the corresponding adjacent tissues, and xenograft tumor tissues were immunohistochemically stained with anti-SASH1 (NBP1-26650, Novus or A302-265A-1, Bethyl Laboratories), anti-MAP4K4 (A301-502A, Bethyl Laboratories or NB100-74630, Novus), anti-Ki67 (27309-1-AP, Proteintech), anti-p53, anti-ERα, and anti-progesterone receptor (PGR) antibodies.

Techniques: Expressing, Immunohistochemistry, Software, Construct, Western Blot