Journal: Cell Reports Medicine
Article Title: Targeting TPX2-dependent lineage plasticity by CDK4/6 inhibition reverses therapy resistance in neuroendocrine bladder carcinoma
doi: 10.1016/j.xcrm.2026.102712
Figure Lengend Snippet: Mapping reveals TPX2 as a representative and functionally relevant driver of NE-like cells (A) Violin plot showing correlations between NE-like cell top markers and the NE-like Sig score across multiple BLCA transcriptomic cohorts. TPX2, highlighted in red, shows the strongest correlation among the markers analyzed. (B and C) Spatial transcriptomic analysis showing the expression of TPX2 and NE-like Sig scores across spatial locations in bladder tumor tissue (B) and their positive correlation (C). R indicates the Spearman correlation coefficient. (D) Representative mIF image of NEBC tissue showing TPX2 (magenta), INSM1 (cyan), and DAPI (blue). The inset highlights TPX2 + (red arrowheads) and INSM1 + (white arrowheads) cells, which demonstrated minimal colocalization. Scale bars, 50 μm. (E and F) Representative mIF images (E) and quantification (F) showing the proportion of TPX2 + panCK + tumor cells across different tumor grades (Tis/Ta/T1: n = 55; T2: n = 46; T3: n = 43; T4: n = 35). Scale bars, 50 μm. (G and H) Flow cytometry (G) and quantification (H) showing the proportions of T24 and UM-UC-3 cells in different cell cycle phases 48 h after transfection with control siRNA or TPX2 siRNA ( n = 3 per group). (I and J) Flow cytometry (I) and quantification (J) showing the proportions of T24 and UM-UC-3 cell lines in different cell cycle phases in the empty vector control and TPX2-oe groups ( n = 3 per group). (K) qPCR analysis was performed to evaluate changes in the expression levels of NE markers following TPX2 knockdown in the T24 cell line. The data are presented as the means ± SDs in (H, J, and K). The box inside violin plot (A) represents the interquartile range (IQR), with the middle line as the median and the hinges corresponding to the 25th and 75th percentiles. p values were determined by one-way ANOVA in (F, H, and K) and by two-tailed unpaired Student’s t test in (J).
Article Snippet: UM-UC-3 , ATCC , RRID: CVCL_1783.
Techniques: Expressing, Flow Cytometry, Transfection, Control, Plasmid Preparation, Knockdown, Two Tailed Test