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Supplementary Figure 3 from Distinct FAK Activities Determine Progenitor and Mammary Stem Cell Characteristics
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posted on 2023-03-30, 21:54 authored by Ming Luo, Xiaofeng Zhao, Song Chen, Suling Liu, Max S. Wicha, Jun-Lin GuanPDF file, 492K, Genotyping of recipient mammary fat pads following transplantation as well as TUNEL assay for luminal and basal acini sections derived from Ctrl, MFCKO, and MFCKD mice.
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ARTICLE ABSTRACT
Mammary stem cells (MaSC) and progenitor cells are important for mammary gland development and maintenance and may give rise to mammary cancer stem cells (MaCSC). Yet, there remains limited understanding of how these cells contribute to tumorigenesis. Here, we show that conditional deletion of focal adhesion kinase (FAK) in embryonic mammary epithelial cells (MaEC) decreases luminal progenitors and basal MaSCs, reducing their colony-forming and regenerative potentials in a cell-autonomous manner. Loss of FAK kinase activity in MaECs specifically impaired luminal progenitor proliferation and alveologenesis, whereas a kinase-independent activity of FAK supported ductal invasion and basal MaSC activity. Deficiency in luminal progenitors suppressed tumorigenesis and MaCSC formation in a mouse model of breast cancer. In contrast with the general inhibitory effect of FAK attenuation, inhibitors of FAK kinase preferentially inhibited proliferation and tumorsphere formation of luminal progenitor-like, but not MaSC-like, human breast cancer cells. Our findings establish distinct kinase-dependent and -independent activities of FAK that differentially regulate luminal progenitors and basal MaSCs. We suggest that targeting these distinct functions may tailor therapeutic strategies to address breast cancer heterogeneity more effectively. Cancer Res; 73(17); 5591–602. ©2013 AACR.Usage metrics
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