Elizabeth R. Smith

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Lineage-committed cells of many tissues exhibit substantial plasticity in contexts such as wound healing and tumorigenesis, but the regulation of this process is not well understood. We identified the Hippo transducer WWTR1/TAZ in a screen of transcription factors that are able to prompt lineage switching of mammary epithelial cells. Forced expression of(More)
In response to retinoic acid, embryonic stem and carcinoma cells undergo differentiation to embryonic primitive endoderm cells, accompanied by a reduction in cell proliferation. Differentiation does not reduce the activation of cellular MAPK/Erk, but does uncouple mitogen-activated protein kinase (MAPK) activation from phosphorylation/activation of Elk-1(More)
BACKGROUND The MAPK/ERK1/2 serine kinases are primary mediators of the Ras mitogenic signaling pathway. Phosphorylation by MEK activates MAPK/ERK in the cytoplasm, and phospho-ERK is thought to enter the nucleus readily to modulate transcription. PRINCIPAL FINDINGS Here, however, we observe that in primary cultures of breast and ovarian epithelial cells,(More)
BACKGROUND The family of zinc finger-containing GATA transcription factors plays critical roles in cell lineage specification during early embryonic development and organ formation. GATA4 and GATA6 were found to be frequently lost in ovarian cancer, and the loss is proposed to account for dedifferentiation of the cancer cells. METHODOLOGY/PRINCIPAL(More)
Disabled-2 (Dab2) is an endocytic adaptor protein involved in clathrin-mediated endocytosis and cargo trafficking. Since its expression is lost in several cancer types, Dab2 has been suggested to be a tumor suppressor. In vitro studies indicate that Dab2 establishes epithelial cell polarity and organization by directing endocytic trafficking of membrane(More)
DESPITE SIGNIFICANT UNDERSTANDING OF THE GENETIC MUTATIONS INVOLVED IN OVARIAN EPITHELIAL CANCER AND ADVANCES IN GENOMIC APPROACHES FOR EXPRESSION AND MUTATION PROFILING OF TUMOR TISSUES, SEVERAL KEY QUESTIONS IN OVARIAN CANCER BIOLOGY REMAIN ENIGMATIC: the mechanism for the well-established impact of reproductive factors on ovarian cancer risk remains(More)
Disabled-2 (Dab2) is a clathrin and cargo binding endocytic adaptor protein, and cell biology studies revealed that Dab2 plays a role in cellular trafficking of a number of transmembrane receptors and signaling proteins. A PTB/PID domain located in the N-terminus of Dab2 binds the NPXY motif(s) present at the cytoplasmic tails of certain transmembrane(More)
Disabled-2 (Dab2) is a widely expressed clathrin binding endocytic adaptor protein and known for the endocytosis of the low-density lipoprotein (LDL) family receptors. Dab2 also modulates endosomal Ras/MAPK (Erk1/2) activity by regulating the disassembly of Grb2/Sos1 complexes associated with clathrin-coated vesicles. We found that the most prominent(More)
The Cancer Atlas project has shown that p53 is the only commonly (96 %) mutated gene found in high-grade serous epithelial ovarian cancer, the major histological subtype. Another general genetic change is extensive aneuploidy caused by chromosomal numerical instability, which is thought to promote malignant transformation. Conventionally, aneuploidy is(More)
Disabled-2 (Dab2) is a widely expressed endocytic adaptor that was first isolated as a 96 KDa phospho-protein, p96, involved in MAPK signal transduction. Dab2 expression is lost in several cancer types including breast cancer, and Dab2 is thought to have a tumor suppressor function. In mammary epithelia, Dab2 was induced upon pregnancy and further elevated(More)