Cross-talk between AMPK and EGFR dependent Signaling in Non-Small Cell Lung Cancer

Sci Rep. 2016 Jun 9:6:27514. doi: 10.1038/srep27514.

Abstract

Lung cancers globally account for 12% of new cancer cases, 85% of these being Non Small Cell Lung Cancer (NSCLC). Therapies like erlotinib target the key player EGFR, which is mutated in about 10% of lung adenocarcinoma. However, drug insensitivity and resistance caused by second mutations in the EGFR or aberrant bypass signaling have evolved as a major challenge in controlling these tumors. Recently, AMPK activation was proposed to sensitize NSCLC cells against erlotinib treatment. However, the underlying mechanism is largely unknown. In this work we aim to unravel the interplay between 20 proteins that were previously associated with EGFR signaling and erlotinib drug sensitivity. The inferred network shows a high level of agreement with protein-protein interactions reported in STRING and HIPPIE databases. It is further experimentally validated with protein measurements. Moreover, predictions derived from our network model fairly agree with somatic mutations and gene expression data from primary lung adenocarcinoma. Altogether our results support the role of AMPK in EGFR signaling and drug sensitivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / metabolism
  • Adenocarcinoma of Lung
  • Antineoplastic Agents / pharmacology
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm / drug effects
  • ErbB Receptors / metabolism*
  • Erlotinib Hydrochloride / pharmacology
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism*
  • Mutation / drug effects
  • Protein Interaction Maps / drug effects
  • Protein Kinase Inhibitors / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • ErbB Receptors
  • AMP-Activated Protein Kinases