Journal: bioRxiv
Article Title: Spatial mapping of proteins and their activity states in cancer models by multiplex in situ PLA
doi: 10.1101/2025.07.11.662357
Figure Lengend Snippet: In A) Sk-BR-3 human HER2-positive breast-carcinoma cells were stimulated with epidermal growth factor (EGF; 50 ng/ml) for 60 min, or left either serum-starved (Starvation control) or in complete-media control conditions; whole-cell lysate from K562 cells was loaded as a positive control in the right-most lane. Immunoblots were probed sequentially for STAT3 (≈70 kDa; Abcam, ab171359, 1:2 000), STAT5A (≈80 kDa; Abcam, ab213219, 1:1 000), ERK2 (≈42 kDa; Thermo Fisher, PA5-29636, 1:1 000), MEK1 (≈45 kDa; Abcam, ab239802, 1:1 000), AKT2 (≈55 kDa; Thermo Fisher, PA5-85518, 1:1 000), phospho-STAT3-Tyr705 (pSTAT3, ≈90–115 kDa; R&D, AF4607, 1:2 000) and pan-AKT (≈60 kDa; CST, #4691, 1:1 000). Membranes were finally reprobed for GAPDH (≈37 kDa; CST, #14C10, 1:1 000) and vinculin (≈120 kDa; CST, #E1E9V, 1:1 000) as loading controls. Molecular-weight markers are indicated on the left. For all panels, proteins were resolved on Bis-Tris SDS–PAGE gels (4–12 % or 10 % as specified in Methods) using MES or MOPS running buffer, transferred to PVDF, and detected by near-infrared fluorescence on a LI-COR Odyssey® imager. In B) estimated relative band intensities of key signaling proteins in Sk-BR-3 and K562 cells are shown. Fluorescence-based Western blot images (Supp (A)) were used to visually estimate band intensities of STAT3, phospho-STAT3 (Tyr705), STAT5A, ERK2, MEK1, AKT2, and pan-AKT in Sk-BR-3 cells under three conditions: serum starvation, complete media, and 60 min EGF treatment, and in K562 cells as a positive control. Band intensities were approximated by visual comparison of signal brightness and normalized to the corresponding housekeeping protein (GAPDH or vinculin) within each lane. Normalized values were plotted as grouped bar graphs to highlight relative abundance patterns across conditions. This semi-quantitative representation supports qualitative comparison and was not derived from raw densitometry. validates the antibody specificity and establishes the baseline expression of PLA target proteins in Sk-BR-3 and K562 cells. Panel A displays the Western blot images of Sk-BR-3 cells subjected to three conditions: serum starvation, complete media (control), and EGF stimulation for 60 minutes. K562 cell lysate is included as a positive control. Panel B presents the quantified band intensities, normalised to the housekeeping proteins GAPDH or vinculin and expressed as percentages. In Sk-BR-3 cells, total STAT3, ERK2, MEK1, AKT2, and pan-AKT were consistently detected across all conditions. STAT3 levels remained stable, while phosphorylation at Tyr705 (pSTAT3) dropped to undetectable levels under serum starvation, rose slightly under media control, and reached higher levels after 60 min of EGF treatment. This trend suggests growth-factor-responsive STAT3 activation despite unchanged total STAT3 levels. MEK1 and AKT2 expression decreased mildly in media control compared to both EGF and starvation conditions, while ERK2 and pan-AKT remained constant. STAT5A was not detected in any Sk-BR3 condition. In contrast, the K562 lysate showed robust STAT5A expression, confirming its hematopoietic lineage specificity. STAT3 was present at lower levels relative to Sk-BR-3 media control, while ERK2 and pan-AKT were comparable between both cell types. MEK1 and AKT2 appeared at slightly lower levels in K562 cells. GAPDH and vinculin levels were consistent across all samples, confirming equal loading and transfer quality. Together, these results confirm the specificity of each antibody, the absence of non-specific binding, and the suitability of both Sk-BR-3 and K562 cells as models for downstream proximity ligation assays aimed at monitoring dynamic signalling interactions.
Article Snippet: The following primary antibodies were used for Western blotting: JAK1 (ProteinTech, 66466-1-Ig), STAT3 (ProteinTech, 60199-1-Ig; Abcam, ab171359), MEK1 (Abcam, ab239802), EGFR (Abcam, ab271834), AKT2 (Thermo Scientific, PA5-85518), ERK2 (Thermo Fisher, PA5-29636), phospho-PI3K p85/p55 (Cell Signaling Technology, 4228S), pSTAT3-Y705 (R&D Systems, AF4607), Grb2 (R&D Systems, mab38461), GAPDH (CST, 14C10), and Vinculin (CST, E1E9V), used at either 1:1000 or 1:2000 dilution.
Techniques: Control, Positive Control, Western Blot, Molecular Weight, SDS Page, Fluorescence, Comparison, Derivative Assay, Expressing, Phospho-proteomics, Activation Assay, Binding Assay, Ligation