CAPZA2 and Human Lung Cancer Progression
Abstract
The goal of this proposal is to examine whether F-actin-capping protein subunit alpha-2 (CAPZA2) plays a role in non-small cell lung cancer (NSCLC) progression and metastasis. More specifically, the proposed studies will examine whether CAPZA2 expression in human NSCLC cell lines will regulate cell properties associated with cell proliferation and motility, including cell migration and invasion in vitro as well as tumor growth and metastasis in mice. Lung cancer is the leading cause of cancer related death for both men and women in the United States with an annual mortality that exceeds breast, prostate, and colorectal cancers combined. Unfortunately, current therapies are ineffective, since approximately 74% of lung cancer patients die within 5 years of diagnosis. NSCLC represents about 80% of all lung cancers. Since the prognosis for patients with NSCLC is poor, identification of new therapeutic targets is urgently needed. Using cBio Cancer Genomics Portal (an open-access resource for interactive exploration of multidimensional cancer genomics data sets), we observed that CAPZA2 gene amplification strongly correlates with poor survival in patients with lung adenocarcinoma, a major subset of NSCLC. Interestingly, in contrast to CAPZA2, no such correlation exists for two other members of CAPZA gene family (CAPZA1 and CAPZA3). Thus, CAPZA2 might promote progression of NSCLC in patients. This proposal addresses the Lung Cancer Research Program 2021 Area of Interest, Understand the molecular mechanisms of initiation and progression to clinically significant lung cancer. This research will establish the basis for more detailed studies aimed at determining the precise molecular mechanisms underlying progression and metastasis of human NSCLC by CAPZA2. Due to the basic nature of this research in its current stage, it is estimated (to the best of our ability) that it may take at least five years to achieve clinically relevant outcome. Successful outcome of this study will potentially lead to development of novel therapeutic approaches targeting CAPZA2 either alone or in combination with existing treatments in patients with NSCLC to combat the progression of lung cancer. This research will likely advance the field of lung cancer via contributing to better understanding the molecular mechanisms that lead to various subtypes of lung cancer. Given that lung cancer disproportionately affects military Veterans and, within this group, lung cancer incidence is not only higher than in the civilian population but also survival rates are lower; the outcome of this research may ultimately have a significant impact on reducing lung cancer mortality in military Service Members, Veterans, and their dependents.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210012
Entities
People
- Grzegorz Sowa
Organizations
- Curators of the University of Missouri
- United States Army