Profiling of subcellular EGFR interactome reveals hnRNP A3 modulates nuclear EGFR localization

Abstract

The aberrant subcellular translocation and distribution of epidermal growth factor receptor (EGFR) represent a major yet currently underappreciated cancer development mechanism in non-small cell lung cancer (NSCLC). In this study, we investigated the subcellular interactome of EGFR by using a spectral counting-based approach combined with liquid chromatography-tandem mass spectrometry to understand the associated protein networks involved in the tumorigenesis of NSCLC. A total of 54, 77, and 63 EGFR-interacting proteins were identified specifically in the cytosolic, mitochondrial, and nuclear fractions from a NSCLC cell line, respectively. Pathway analyses of these proteins using the KEGG database shown that the EGFR-interacting proteins of the cytosol and nucleus are involved in the ribosome and spliceosome pathways, respectively, while those of the mitochondria are involved in metabolizing propanoate, fatty acid, valine, leucine, and isoleucine. A selected nuclear EGFR-interacting protein, hnRNP A3, was found to modulate the accumulation of nuclear EGFR. Downregulation of hnRNP A3 reduced the nuclear accumulation of EGFR, and this was accompanied by reduced tumor growth ability in vitro and in vivo. These results indicate that variations in the subcellular translocation and distribution of EGFR within NSCLC cells could affect tumor progression.

Facilitating GL13K Peptide Grafting on Polyetheretherketone via 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide: Surface Properties and Antibacterial Activity

“…The pristine and coated PEEK samples were immersed in DI water for 24 h, and the morphologies and chemical compositions of these samples were determined. The supernatant water was analyzed after the immersion test for peptide concentration, according to the HPLC-MS/MS procedure described in [ 46 , 47 ], except that a precursor ion quantifier node using dimethyl quantification was employed.…”

Effect of EGFR on SQSTM1 Expression in Malignancy and Tumor Progression of Oral Squamous Cell Carcinoma

“…EGFR mostly functions on the cell membrane since it can traffic to the cytoplasm or other subcellular organelles [30]. Different sub-localizations of EGFR may exert different functions for cancer progression [31].…”

hnRNP A/B Proteins: An Encyclopedic Assessment of Their Roles in Homeostasis and Disease

“…A3 and EGFR are both increased in expression in human lung cancers [254,259]. In cell culture studies, A3 interacted with nuclear EGFR [260], while its depletion also reduced EGFR nuclear localization [259]. This suggests that abundant A3 promotes EGFR nuclear accumulation and oncogene transcription.…”

“…A3 has been found to interact with Sox-2, one of the Yamanaka factors required to induce stem cell pluripotency, but the outcome of this interaction was not explored [258]. The interaction between A3 and EGFR (epidermal growth factor receptor) is somewhat better-characterized: EGFR relocalizes to intracellular locations in response to stimuli like radiation and ligand binding, and when nuclear, can act as a transcriptional activator of oncoproteins like cMyc, Cyclin D1, and COX2 [259]. A3 and EGFR are both increased in expression in human lung cancers [254,259].…”

“…The interaction between A3 and EGFR (epidermal growth factor receptor) is somewhat better-characterized: EGFR relocalizes to intracellular locations in response to stimuli like radiation and ligand binding, and when nuclear, can act as a transcriptional activator of oncoproteins like cMyc, Cyclin D1, and COX2 [259]. A3 and EGFR are both increased in expression in human lung cancers [254,259]. In cell culture studies, A3 interacted with nuclear EGFR [260], while its depletion also reduced EGFR nuclear localization [259].…”