Figure 8. SNAIL protein expression level is positively correlated with lymph node invasion and negatively correlated with FBXO11 expression level in breast cancer patients.
(A) Correlation study of SNAIL expression level with lymph node invasion in 136 breast tumor specimens. SNAIL-lo: SNAIL IHC staining lower than median; SNAIL-hi: SNAIL IHC staining higher than median; LN-: without lymph node invasion; LN+: with lymph node invasion. χ2=4.9, p = 0.026 by chi-square test. (B) Kaplan-Meier plots of distant relapse-free survival of patients, stratified by expression of PKD1. Data obtained from the Kaplan-Meier plotter database (Gyorffy et al., 2010). (C) Correlation study of activated PKD1 (pY95-PKD1) and S11-SNAIL in a breast tumor tissue microarray (US Biomax BC081120), χ2=10.0, p = 0.0016 by chi-square test. (D) Representative IHC images of pY95-PKD1 and pS11 -SNAIL in breast tumors. Scale bars, 100µm. (E) Correlation study of SNAIL and FBXO11 in the same breast tumor tissue microarray. χ2=7.49, p = 0.0062 by chi-square test. (F) Representative IHC images of SNAIL and FBXO11 in breast tumors. Scale bars: 100µm. (G) Schematic model for PKD1-dependent SNAIL protein ubiquitylation and degradation by FBXO11. SNAIL protein is first phosphorylated by PKD1 kinase at Serine-11 residue before it can be recognized and ubiquitylated by SCF-FBXO11 E3 ligase complex. Poly-ubiquitylated SNAIL protein is then degraded through 26S proteosomal degradation pathway.