Fig. 7: CTSD-deficient tumors overcome the initial growth arrest independent of somatic mutations. | Nature Communications

Fig. 7: CTSD-deficient tumors overcome the initial growth arrest independent of somatic mutations.

From: Cathepsin D deficiency in mammary epithelium transiently stalls breast cancer by interference with mTORC1 signaling

Fig. 7

a Time from first palpation to end-stage for tumors of PyMT mice of indicated genotypes (n = 12 animals for controls (4× Ctsd+/fl + 8× Ctsdfl/fl), n = 10 animals for MMTV-cre;Ctsd−/−). b Metastatic burden in lungs from PyMT mice of indicated genotypes with end-stage tumors (n = 12 animals for controls (4× Ctsd+/fl + 8× Ctsdfl/fl), n = 10 animals for MMTV-cre;Ctsd−/−). c Proportion of different types of somatic and loss of heterozygosity (LOH) mutations detected by whole exome sequencing in tumors from 18-week-old PyMT mice of indicated genotypes (Controls: Ctsdfl/fl; n = 4 animals). d Circos plots showing mutations from c along the chromosomes per individual control (left) and MMTV-cre;Ctsd−/− (right) tumor (represented as separate concentric rings). Deletion of Ctsd exon 2 is highlighted in red. Continuous gray lines mark positions of homologs of frequently mutated genes in human breast cancer. e Pictures of unstained (left) and acidic β-galactosidase-stained (right) Ctsd+/+ (top) and Ctsd−/− (bottom) PyMT cells cultured for ≥8 weeks in 1% FCS medium (1% FCS LT). Compare to Fig. 3a, b for short-term 1% FCS Ctsd+/+ and Ctsd−/− PyMT cells. Bars, 50 μm. Representative of 2 independent experiments. f Quantification of label-retaining cells among 1% FCS LT Ctsd+/+ and Ctsd−/− PyMT cells (n = 6 independent experiments; two-sided two-sample t-test). Short-term conditions (10% FCS, 1% FCS) as presented in Fig. 3c are included for convenient comparison. Bar charts show all data points with mean + SD and p-value. Source data are provided as a Source Data file.

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