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Stem Cell Determinant SOX9 Promotes Lineage Plasticity and Progression in Basal-like Breast Cancer.

Cell reports (2020-06-11)
John R Christin, Chunhui Wang, Chi-Yeh Chung, Yu Liu, Christopher Dravis, Wei Tang, Maja H Oktay, Geoffrey M Wahl, Wenjun Guo

Lineage plasticity is important for the development of basal-like breast cancer (BLBC), an aggressive cancer subtype. While BLBC is likely to originate from luminal progenitor cells, it acquires substantial basal cell features and contains a heterogenous collection of cells exhibiting basal, luminal, and hybrid phenotypes. Why luminal progenitors are prone to BLBC transformation and what drives luminal-to-basal reprogramming remain unclear. Here, we show that the transcription factor SOX9 acts as a determinant for estrogen-receptor-negative (ER-) luminal stem/progenitor cells (LSPCs). SOX9 controls LSPC activity in part by activating both canonical and non-canonical nuclear factor κB (NF-κB) signaling. Inactivation of TP53 and RB via expression of SV40 TAg in a BLBC mouse tumor model leads to upregulation of SOX9, which drives luminal-to-basal reprogramming in vivo. Furthermore, SOX9 deletion inhibits the progression of ductal carcinoma in situ (DCIS)-like lesions to invasive carcinoma. These data show that ER- LSPC determinant SOX9 acts as a lineage plasticity driver for BLBC progression.

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Red Blood Cell Lysing Buffer Hybri-Max, liquid, sterile-filtered, suitable for hybridoma
β-Glycerophosphate disodium salt hydrate, BioUltra, suitable for cell culture, suitable for plant cell culture, ≥99% (titration)
Immobilon-P PVDF Membrane, 1 roll, 26.5 cm x 3.75 m, 0.45 µm pore size, Hydrophobic PVDF Transfer Membrane for western blotting.
Sodium orthovanadate, ≥90% (titration)
Sodium orthovanadate, 99.98% trace metals basis
TruPAGE Precast Gels, 4-12%, 10 x 10cm, 12-well
TruPAGE Tris-MOPS SDS Express Running Buffer, 20 ×

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