Physical properties of HPV positive senescent cells
Cellular senescence is defined as the finite proliferative lifespan of somatic cells where repeated cell division results in an irreversible arrest of cellular growth yet continued metabolic activity. The presence of senescent cells is a hallmark of premalignant lesions but lost in malignancies, and intact senescence pathways are important for optimal response to chemotherapy. In this way, senescence is widely considered a tumor suppressive process, but when in excess may also contribute to the disruption of tissue homeostasis and organismal aging. As a double edged sword, much remains to be learned about the molecular properties and functions of senescent cells.
Human papillomavirus encodes two oncogenes E6 and E7 which are responsible for the initiation and maintainance of malignant transformation. The targeting of E6 and E7 in HPV positive cancer cells leads to the re-activation of the cellular tumor suppressors p53 and Rb, and subsequent synchronized senescence induction. E6/E7 interference tools used in our laboratory might therefore be promising for the treatment of HPV-positive cancers. Examination of the physical and motility properties of senescent HeLa cells has recently identified uniquely stimulated migratory and invasive phenotypes. These could be physiologically important in the context of the developing or adult organism, or as a component of the premalignant tumor microenvironment. Current 2D videomicroscopy together with biochemical analyses are designed to identify underlying molecular pathways and study the role of senescent cell motility in cell and animal studies
