Download 2015 department of medicine research day

2015 DEPARTMENT OF MEDICINE RESEARCH DAY
Title of Poster: Over-expression of Slug leads to malignant transformation in an in
vitro model of pulmonary premalignancy.
Presenter: Brandon S. Grimes
Division: Pulmonary and Critical Care Medicine
☐Faculty ☒Fellow ☐Resident ☐Post-doc Research Fellow ☐Graduate Student ☐Medical Student ☐Other
Principal Investigator/Mentor: Steven M. Dubinett
Co-Investigators: Tonya C. Walser, Linh Tran, Rui Li, Zhe Jing
Thematic Poster Category: Development, Morphogenesis, Cell Growth and Differentiation, Apoptosis, Stem Cell Biology,
Carcinogenesis and Cancer Biology
Abstract
With the implementation of lung cancer screening programs, the detection of premalignant lung
lesions is on the rise. A better understanding of the mechanisms underlying progression of
premalignant lesions to non-small cell lung cancer (NSCLC) could lead to the development of new
prevention and treatment strategies.
Slug (SNAI2) is a member of the Snail family of zinc finger transcription factors that are known to play
a key role in epithelial-mesenchymal transition (EMT), which is a signaling program requisite for
cancer cell invasion and metastasis. Recent research has shown that patients with lung
adenocarcinoma tumors characterized by Slug up-regulation have an increased likelihood of
recurrence and poor survival. In Slug over-expressing lung cancer cell lines, increased tumorigenesis
and invasiveness have been observed. The role of Slug in premalignancy and early stage lung cancer,
however, has not been explored.
We established several NSCLC and human bronchial epithelial cells (HBEC) lines with ectopic stable
over-expression of Slug. Via western blot analysis, the cells demonstrate a mesenchymal phenotype,
confirming Slug-mediated induction of EMT in both cell types. Proliferation rates determined by using
an ATP luminescence-based assay were not significantly different between Slug over-expressing and
control cell lines. However, we determined that the Slug over-expressing cancer cells and HBECs have
increased anchorage-independent growth, the in vitro correlate of tumorigenicity in murine models.
These findings suggest that Slug may have a role in the initiation and progression of early stage
NSCLC. Presently, our focus is to determine the mechanisms underlying this Slug-dependent
transformation by molecularly profiling the cells. As a clinical correlate, we are also evaluating Slug
expression in human premalignant lung lesions, such as atypical adenomatous hyperplasia (AAH) and
adenocarcinoma in situ (AIS), identified in our existing human lung cancer tissue repository.