Proteomic signatures associated with p53 mutational status in lung adenocarcinoma
Abstract
p53 is commonly mutated in lung adenocarcinoma. Mutant p53 loses wild‐type function and some missense mutations further acquire oncogenic functions, while p53 wild‐type may also induce pro‐survival signaling. Therefore identification of signatures based on p53 mutational status has relevance to our understanding of p53 signaling pathways in cancer and identification of new therapeutic targets. To this end, we compared proteomic profiles of three cellular compartments (whole‐cell extract, cell surface, and media) from 28 human lung adenocarcinoma cell lines that differ based on p53 mutational status. In total, 11 598, 11 569, and 9090 protein forms were identified in whole‐cell extract, cell surface, and media, respectively. Bioinformatic analysis revealed that representative pathways associated with epithelial adhesion, immune and stromal cells, and mitochondrial function were highly significant in p53 missense mutations, p53 loss and wild‐type p53 cell lines, respectively. Of note, mRNA levels of peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC1‐α), a transcription coactivator that promotes mitochondrial oxidative phosphorylation and mitochondrial biogenesis, was substantially higher in p53 wild‐type cell lines compared to either cell lines with p53 loss or with missense mutation. Small interfering RNA targeting PGC1‐α inhibited cell proliferation in p53 wild‐type cell lines, indicative of PGC1‐α and its downstream molecules as potential therapeutic targets in p53 wild‐type lung adenocarcinoma.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 20, 2014
- Source ID
- 10.1002/pmic.201400378
Entities
People
- Adi F. Gazdar
- Ayumu Taguchi
- Hiroyuki Katayama
- Hong Wang
- Müge Çeliktaş
- Oliver Delgado
- Samir M Hanash
Organizations
- Canary Foundation
- LUNGevity Foundation
- National Cancer Institute
- United States Department of Defense
- University of Texas at Austin