Related Experiment Video
Updated: Jun 17, 2026
Phosphoproteomic Strategy for Profiling Osmotic Stress Signaling in Arabidopsis
Published on: June 25, 2020
Phosphoproteomic profiling of arsenite-treated human small airway epithelial cells
1Centre for Radiological Research, Columbia University, New York, NY 10032, USA. gw2154@columbia.edu
Abstract:
Arsenic is well documented as a chemotherapeutic agent capable of inducing cell death; however, it is also considered as a human carcinogen. Although it has recently been shown that arsenite exposure can potentiate genotoxicity, little is known about its global effects exerted in cells at the proteome level. Immortalized human small airway epithelial cells exposed to arsenite were used to identify phosphoproteins of two major signaling cascades, such as the human phospho-receptor tyrosine kinase (Phospho-RTK) and the mitogen-activated protein kinases (MAPKs). These two arrays included several phosphoproteins, such as EGFR, ErbB2, ErbB4, InsulinR, Flt-3, extracellular signal-regulated kinases (ERK1/2), intracellular kinases such as AKT, GSK-3, c-Jun N-terminal kinases (JNK1-3) and different p38 isoforms (alpha/beta/delta/gamma). In arsenite-treated cells, phosphorylation of EGFR, InsulinR and Flt3R showed an increase when compared to their non-arsenite treated counterparts. Inhibitors of these proteins further confirmed the involvement of such proteins in the neoplasm transformation of arsenite-treated human small airway epithelial cells as seen in changes in plating efficiency, anchorage-independent growth and proliferation rate. It can be concluded that analysis of phosphoprotein by using phosphoproteomic profiling can be very useful to understand the mechanism of arsenite-induced carcinogenesis.
Insights
Arsenic exposure increases specific phosphoprotein levels, driving cell changes linked to cancer. Phosphoproteomic profiling helps understand arsenic-induced carcinogenesis mechanisms.
Area of Science:
- Cellular and Molecular Biology
- Cancer Research
- Toxicology
Background:
- Arsenic compounds are known chemotherapeutics but also human carcinogens.
- Arsenite exposure can potentiate genotoxicity, but its proteome-level effects are poorly understood.
- Investigating global cellular effects of arsenite is crucial for understanding carcinogenesis.
Purpose of the Study:
- To identify phosphoproteins affected by arsenite exposure in human small airway epithelial cells.
- To elucidate the role of specific signaling pathways in arsenite-induced neoplasm transformation.
- To explore phosphoproteomic profiling as a tool for understanding arsenic carcinogenesis.
Main Methods:
- Exposure of immortalized human small airway epithelial cells to arsenite.
- Utilized phospho-receptor tyrosine kinase (Phospho-RTK) and mitogen-activated protein kinases (MAPKs) arrays.
- Analyzed changes in protein phosphorylation, plating efficiency, anchorage-independent growth, and proliferation rate.
Main Results:
- Increased phosphorylation of EGFR, InsulinR, and Flt3R observed in arsenite-treated cells.
- Inhibitors targeting these proteins confirmed their involvement in neoplasm transformation.
- Arsenite exposure altered cellular characteristics associated with cancer progression.
Conclusions:
- Phosphoproteomic profiling is valuable for understanding arsenite-induced carcinogenesis.
- Specific receptor tyrosine kinases and their downstream signaling pathways are implicated in arsenite's carcinogenic effects.
- Further research into these pathways can inform strategies to mitigate arsenic-induced cancer risk.
