RAB4A is a master regulator of cancer cell stemness upstream of NUMB-NOTCH signaling.

Cancer stem cells (CSCs) are a group of specially programmed tumor cells that possess the characteristics of perpetual cell renewal, increased invasiveness, and often, drug resistance. Hence, eliminating CSCs is a major challenge for cancer treatment. Understanding the cellular programs that maintain CSCs, and identifying the critical regulators for such programs, are major undertakings in both basic and translational cancer research.

RAB4A GTPase regulates epithelial-to-mesenchymal transition by modulating RAC1 activation.

Epithelial-to-mesenchymal transition (EMT) is a critical underpinning process for cancer progression, recurrence and resistance to drug treatment. Identification of new regulators of EMT could lead to the development of effective therapies to improve the outcome of advanced cancers. In the current study we discovered, using a variety of in vitro and in vivo approaches, that RAB4A function is essential for EMT and related manifestation of stemness and invasive properties.

Reduced PAX2 expression in murine fallopian tube cells enhances estrogen receptor signaling.

High-grade serous ovarian cancer (HGSOC) is thought to progress from a series of precursor lesions in the fallopian tube epithelium (FTE). One of the preneoplastic lesions found in the FTE is called a secretory cell outgrowth (SCOUT), which is partially defined by a loss of paired box 2 (PAX2). In the present study, we developed PAX2-deficient murine cell lines in order to model a SCOUT and to explore the role of PAX2 loss in the etiology of HGSOC.

A strategy to identify a ketoreductase that preferentially synthesizes pharmaceutically relevant (S)-alcohols using whole-cell biotransformation.

Introduction: Chemical industries are constantly in search of an expeditious and environmentally benign method for producing chiral synthons. Ketoreductases have been used as catalysts for enantioselective conversion of desired prochiral ketones to their corresponding alcohol. We chose reported promiscuous ketoreductases belonging to different protein families and expressed them in E.

Prolactin signaling drives tumorigenesis in human high grade serous ovarian cancer cells and in a spontaneous fallopian tube derived model.

The pathways responsible for tumorigenesis of high grade serous ovarian cancer (HGSOC) from the fallopian tube epithelium (FTE) are still poorly understood. A human prolactin (PRL) like gene, Prl2c2 was amplified >100 fold in a spontaneous model of FTE-derived ovarian cancer (MOE - murine oviductal epithelium high passage). Prl2c2 stable knockdown in MOE cells demonstrated a significant reduction in cell proliferation, 2-dimensional foci, anchorage independent growth, and blocked tumor formation.

Programmed Ribosomal Frameshifting Generates a Copper Transporter and a Copper Chaperone from the Same Gene.

Metal efflux pumps maintain ion homeostasis in the cell. The functions of the transporters are often supported by chaperone proteins, which scavenge the metal ions from the cytoplasm. Although the copper ion transporter CopA has been known in Escherichia coli, no gene for its chaperone had been identified.

Cadherin-6 type 2, K-cadherin (CDH6) is regulated by mutant p53 in the fallopian tube but is not expressed in the ovarian surface.

High-grade serous ovarian cancer (HGSOC) is the most lethal gynecological malignancy and may arise in either the fallopian tube epithelium (FTE) or ovarian surface epithelium (OSE). A mutation in p53 is reported in 96% of HGSOC, most frequently at R273 and R248. The goal of this study was to identify specific gene targets in the FTE that are altered by mutant p53, but not in the OSE.

Spontaneous Transformation of Murine Oviductal Epithelial Cells: A Model System to Investigate the Onset of Fallopian-Derived Tumors.

High-grade serous carcinoma (HGSC) is the most lethal ovarian cancer histotype. The fallopian tube secretory epithelial cells (FTSECs) are a proposed progenitor cell type. Genetically altered FTSECs form tumors in mice; however, a spontaneous HGSC model has not been described.

Mutant p53 expression in fallopian tube epithelium drives cell migration.

Ovarian cancer is the fifth leading cause of cancer death among US women. Evidence supports the hypothesis that high-grade serous ovarian cancers (HGSC) may originate in the distal end of the fallopian tube. Although a heterogeneous disease, 96% of HGSC contain mutations in p53.

Effect of codon-optimized E. coli signal peptides on recombinant Bacillus stearothermophilus maltogenic amylase periplasmic localization, yield and activity.

Recombinant proteins can be targeted to the Escherichia coli periplasm by fusing them to signal peptides. The popular pET vectors facilitate fusion of target proteins to the PelB signal. A systematic comparison of the PelB signal with native E.