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Updated: Oct 17, 2025
Quantitative Mass Spectrometric Profiling of Cancer-cell Proteomes Derived From Liquid and Solid Tumors
Published on: February 27, 2015
Protein co-expression network-based profiles revealed from laser-microdissected cancerous cells of lung squamous-cell
Toshihide Nishimura1,2, Kiyonaga Fujii3,4,5, Haruhiko Nakamura3,4
1Department of Translational Medicine Informatics, St. Marianna University School of Medicine, Kawasaki, Kanagawa, 216-8511, Japan. t-nisimura@marianna-u.ac.jp.
Abstract:
No therapeutic targets have been identified for lung squamous cell cancer (SqCC) which is the second most prevalent lung cancer because its molecular profiles remain unclear. This study aimed to unveil disease-related protein networks by proteomic and bioinformatic assessment of laser-microdissected cancerous cells from seven SqCCs compared with eight representative lung adenocarcinomas. We identified three network modules significant to lung SqCC using weighted gene co-expression network analysis. One module was intrinsically annotated to keratinization and cell proliferation of SqCC, accompanied by hypoxia-induced aerobic glycolysis, in which key regulators were activated (HIF1A, ROCK2, EFNA1-5) and highly suppressed (KMT2D). The other two modules were significant for translational initiation, nonsense-mediated mRNA decay, inhibited cell death, and interestingly, eIF2 signaling, in which key regulators, MYC and MLXIPL, were highly activated. Another key regulator LARP1, the master regulator in cap-dependent translation, was highly suppressed although upregulations were observed for hub proteins including EIF3F and LARP1 targeted ribosomal proteins, among which PS25 is the key ribosomal protein in IRES-dependent translation. Our results suggest an underlying progression mechanism largely caused by switching to the cap-independent, IRES-dependent translation of mRNA subsets encoding oncogenic proteins. Our findings may help to develop therapeutic strategies to improve patient outcomes.
Insights
Lung squamous cell cancer (SqCC) progression may involve a shift to cap-independent translation of oncogenic proteins. This discovery offers potential new therapeutic targets for SqCC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Lung squamous cell cancer (SqCC) lacks identified therapeutic targets due to unclear molecular profiles.
- SqCC is the second most common type of lung cancer.
Purpose of the Study:
- To identify disease-related protein networks in SqCC.
- To compare molecular profiles of SqCC with lung adenocarcinoma.
Main Methods:
- Proteomic and bioinformatic analysis of laser-microdissected SqCC and lung adenocarcinoma cells.
- Weighted gene co-expression network analysis (WGCNA) to identify significant network modules.
Main Results:
- Three significant network modules identified in SqCC.
- One module linked to keratinization, proliferation, and hypoxia-induced glycolysis (activated: HIF1A, ROCK2; suppressed: KMT2D).
- Two modules associated with translational initiation, mRNA decay, cell death inhibition, and eIF2 signaling (activated: MYC, MLXIPL; suppressed: LARP1).
- Upregulation of eIF3F and LARP1-targeted ribosomal proteins (e.g., PS25) suggests a shift to IRES-dependent translation.
Conclusions:
- SqCC progression may be driven by a switch to cap-independent, IRES-dependent translation of oncogenic mRNAs.
- Findings may inform the development of novel therapeutic strategies for SqCC.
- Identification of key regulators (HIF1A, MYC, MLXIPL, LARP1) provides potential therapeutic targets.
