ABSTRACT
Epigenetic regulation of gene expression is a fundamental determinant of molecular and cellular function, and epigenetic reprogramming in the context of cancer has emerged as one of the key enabling characteristics associated with acquisition of the core hallmarks of this disease. As such, there has been renewed interest in studying the role of transcription factors as epigenetic regulators of gene expression in cancer. In this review, we discuss the current state of knowledge surrounding the oncogenic functions of FOXC2, a transcription factor that frequently becomes dysregulated in a variety of cancer types. In addition to highlighting the clinical impact of aberrant FOXC2 activity in cancer, we discuss mechanisms by which this transcription factor becomes dysregulated in both tumor and tumor-associated cells, placing particular emphasis on the ways in which FOXC2 promotes key hallmarks of cancer progression. Finally, we bring attention to important issues related to the oncogenic dysregulation of FOXC2 that must be addressed going forward in order to improve our understanding of FOXC2-mediated cancer progression and to guide prognostic and therapeutic applications of this knowledge in clinical settings.
Subject(s)
Epithelial-Mesenchymal Transition , Neoplasms , Humans , Epithelial-Mesenchymal Transition/genetics , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/metabolism , Epigenesis, Genetic , Neoplasms/geneticsABSTRACT
The Barnes maze is a reliable measure of spatial learning and memory that does not require food restriction or exposure to extremely stressful stimuli. The Barnes maze can also assess other mouse behaviors, such as general motivation to escape from the maze platform and exploratory behavior. The Barnes maze can measure whether a genetic mutation or environmental variable can impact the acquisition and retention of spatial memories, as well as provide information about the search strategy employed by the mice. Here we use the Barnes maze to detect a memory deficit in adult mice following a single developmental ethanol exposure event. The newly described Damsel-in-Distress paradigm exposes a male mouse to a female mouse trapped in a chamber in the open center field of the arena. It provides an opportunity for the mouse to socially respond to the trapped female and exhibit prosocial behavior. The Damsel-in-Distress paradigm can also be used to examine mouse behavior in a novel arena and measure locomotor activity. Both the Barnes Maze and the Damsel-in-Distress protocols require minimal financial investment and most aspects of the tests can be constructed from common lab supplies. These flexible and accessible tools can also be used to detect behavioral changes over the course of development.