Quantifying cancer- and drug-induced changes in Shannon information capacity of RTK signaling

Area of Science:

• Cellular signaling and information theory
• Quantitative analysis of biological systems

Background:

• Cellular signaling pathways transmit external cues for accurate cell response.
• Cancer can impair signal transmission, but the impact on information capacity is unquantified.

Purpose of the Study:

• To quantify and compare information capacity in receptor tyrosine kinase (RTK) signaling pathways.
• To assess the impact of oncogene-driven cancer on cellular information processing.
• To evaluate the efficacy of targeted interventions using information capacity as a metric.

Main Methods:

• Utilized pseudo-random pulsatile optogenetic stimulation and live-cell imaging.
• Applied information theory to measure information rate and channel capacity.
• Employed in silico protocol optimization to estimate maximum information rates.

Main Results:

• RTK/ERK pathway information rate in lung cancer cells (STE-1) was low (<0.5 bit/hour), increasing to 3 bit/hour after oncogene inhibition.
• Information transmission occurred in only 50-70% of cancer cells.
• Oncogene inhibition increased STE-1 cell RTK/ERK pathway capacity to 6 bit/hour, still lower than in healthy BEAS-2B cells (11 bit/hour).
• The RTK/calcineurin pathway in BEAS-2B cells demonstrated a capacity exceeding 15 bit/hour.

Conclusions:

• Information capacity is a sensitive indicator of disease-associated signaling dysfunction.
• Targeted oncogene inhibition can partially restore signaling pathway capacity.
• This approach offers a novel method for evaluating therapeutic interventions in cancer.