The vav proto‐oncogene is universally and specifically expressed in hematopoietic cells. vav contains a unique array of motifs allowing the protein to function as a signal transducer and possibly as a transcription factor. Under certain in vitro culture conditions murine embryonic stem cells develop into colonies containing multiple hematopoietic lineages. In embryonic stem cell lines, constitutively expressing high levels of antisense vav transcripts through a stably integrated transgene, differentiation into hematopoietic cells is disrupted. This observation presents the first evidence that vav has a critical role in the development of hematopoietic cells from totipotent cells.

The contribution of basal and luminal cells to cancer progression and metastasis is poorly understood. We report generation of reporter systems driven by either keratin-14 (K14) or keratin-8 (K8) promoter that not only express a fluorescent protein but also an inducible suicide gene. Transgenic mice express the reporter genes in the right cell compartments of mammary gland epithelia and respond to treatment with toxins. In addition, we engineered the reporters into 4T1 metastatic mouse tumor cell line and demonstrate that K14+ cells, but not K14− or K8+, are both highly invasive in three-dimensional (3D) culture and metastatic in vivo. Treatment of cells in culture, or tumors in mice, with reporter-targeting toxin inhibited both invasive behavior and metastasis in vivo. RNA sequencing (RNA-seq), secretome, and epigenome analysis of K14+ and K14− cells led to the identification of amphoterin-induced protein 2 (Amigo2) as a new cell invasion driver whose expression correlated with decreased relapse-free survival in patients with TP53 wild-type (WT) breast cancer.