Journal: Nature Communications

Article Title: Human ribonuclease 1 serves as a secretory ligand of ephrin A4 receptor and induces breast tumor initiation

doi: 10.1038/s41467-021-23075-2

Figure Lengend Snippet: a , Prognostic correlation of survival analyses of breast cancer patients with high and low hRNase 1 levels. OS, overall survival; RFS, relapse-free survival; DMFS, distant-metastasis-free survival. HR, hazard ratio. b , c Prognostic correlation of the RFS with different grades ( b ) and lymph node statuses ( c ) of patients with breast cancer in the indicated groups with different hRNase 1 levels. LN, lymph node. d Top, plots of IHC scores of hRNase 1 level in breast tumor tissues (T; n = 31) vs normal tissues (N; n = 12) (Pantomics Inc., #BRC961). Bottom, representative images of IHC staining of hRNase 1 expression in normal and breast tumor tissues. Bar, 25 µm. * p = 0.0188. e Box plots of IHC scores of hRNase 1 level in breast tumor tissues subdivided into four molecular subtypes. Case numbers are shown in the parentheses. f ELISA of hRNase 1 levels in serum samples of breast tumor patients (T; n = 50) compared with noncancerous individuals (N; n = 24). * p = 0.0382. g , ELISA of hRNase 1 levels in breast tumor serum samples subdivided into three molecular subtypes. Case numbers are shown in the parentheses. h Box plots of ELISA of hRNase 1 expression in the conditioned medium (CM) of eight breast cancer cells and two normal cells. KPL4 cell line as an outlier. i Western blotting (WB) of hRNase 1 expression level secreted in breast cancer cells; the experiment was repeated a second time with similar results. * p = 0.0415. Survival data were analyzed using Kaplan-Meier Plotter (Probe: 201785_at) and p values were calculated by Log-rank test ( a – c ). Error bars represent mean ± SD ( f , g ). * p < 0.05, ns, not significant, two-tailed unpaired t test ( d , f , h ), ANOVA analysis ( e , g ). Box plots indicate minima (lower end of whisker), maxima (upper end of whisker), median (center), 25th percentile (bottom of box), and 75th percentile (top of box) ( d , e , h ) as well as outlier (single point) ( h ). Source data are provided as a Source Data file.

Article Snippet: Human breast tumor tissue array was obtained from Pantomics (#BRC961 or #BRC1021).

Techniques: Immunohistochemistry, Expressing, Enzyme-linked Immunosorbent Assay, Western Blot, Two Tailed Test, Whisker Assay

Journal: Nature Communications

Article Title: Human ribonuclease 1 serves as a secretory ligand of ephrin A4 receptor and induces breast tumor initiation

doi: 10.1038/s41467-021-23075-2

Figure Lengend Snippet: a Quantification for the correlation between tissue phospho-EphA4-Y779 and plasma hRNase 1 in the paired breast cancer patients. Chi-squared test. b – d Quantification of IHC staining for the correlation between hRNase 1 and phospho-EphA4-Y779 ( b ), hRNase 1 and CD133 ( c ), and CD133 and phospho-EphA4-Y779 ( d ) by human breast TMA analysis (Pantomics Inc., #BRC1021). Fisher’s exact test. e Two representative cases of IHC staining for ( b – d ). The experiment was performed an additional time with similar results. Bar, 50 μm. f A proposed model of hRNase 1 as a secretory ligand of EphA4 to positively regulate breast tumor initiation. In brief, elevated levels of serum hRNase 1 induces its binding to EphA4 and triggers EphA4 signaling (red stars) in breast tumor cells in an autocrine/paracrine manner, which in turn promotes breast tumor initiation via the IKK/NF-κB and MEK/Erk activating pathways. Such EphA4 activation and CSC-like state triggered by hRNase 1 may be sustained in conjunction with juxtacrine signaling via the classical membrane-bound EphA4 ligands, ephrins. Artwork by H-H.L., Y-N.W., and M-C.H.

Article Snippet: Human breast tumor tissue array was obtained from Pantomics (#BRC961 or #BRC1021).

Techniques: Clinical Proteomics, Immunohistochemistry, Binding Assay, Activation Assay, Membrane

Journal: Oncogene

Article Title: CAIX forms a transport metabolon with monocarboxylate transporters in human breast cancer cells.

doi: 10.1038/s41388-019-1098-6

Figure Lengend Snippet: Fig. 1 CAIX is colocalized with MCT1/4 in human breast tumor tis- sue, but not in healthy breast tissue. a–d, f–i In situ proximity ligation assay (PLA) for CAIX and MCT1 (a–d) or MCT4 (f–i) in grade I (a, f), grade II (b, g), and grade III (c, h) breast tumor tissue, and unin- volved breast tissue (d, i) of human cancer patients. Panels a1–d1, f1–i1

Article Snippet: Human breast tissue micro arrays were purchased from Novus Biological, Wiesbaden, Germany (NBP2–47174).

Techniques: In Situ, Proximity Ligation Assay