Fig. 2: Basal-like cells become invasive in Collagen I and drive collective invasion.
From: A YAP-centered mechanotransduction loop drives collective breast cancer cell invasion
a, b Confocal imaging of Keratin 8 (K8), Keratin 14 (K14) in MMTV-PyMT (a) parental and b monoclonal cultures growing in 3D BME. a) Zoom in show the two subtypes of organoids (i) luminal and (ii) mixed. a, b Arrowheads indicate K14 positive (basal-like) cells located at the organoid-ECM interface. c, d Confocal imaging of MMTV-PYMT parental organoids embedded in 3D Collagen I (reflection). Protrusive K14-positive cells guide multicellular invasive strands. White arrowheads: leader cells, white arrows: Collagen I fiber alignment. Magenta arrowheads: non-protrusive K14-negative cells that are in contact with Collagen I. a–c Representative images from 3 independent experiments. e Percentage of monoclonal organoids showing at least 1 protrusive strand after 3 days in 3D Collagen I (related to d). Average values from n = 97 (mixed) and n = 82 (luminal) organoids per condition from 7 (mixed) and 6 (luminal) independent experiments. Error bars, SD. P values, two-sided unpaired Mann–Whitney test. f UMAP plots based on transcriptional profile from mRNA sequencing of single cells isolated from MMTV-PyMT organoids cultured in 3D BME (799 cells from 3× 386-well plates) or Collagen I (627 cells from 3× 386 plates). Percentage of basal cells of the total amount of cells is indicated in the upper corner of the UMAP plots. g Plots of the same individual cells as (f) with the red/blue color-coded log2 cumulative read counts of basal marker K14. Scale bars: 50 μm (a–d), 25 μm (ai, aii), 10 μm (a–d, inset). Source data are provided as a Source Data file.
