SPIB promotes anoikis resistance via elevated autolysosomal process in lung cancer cells

FEBS J. 2020 Nov;287(21):4696-4709. doi: 10.1111/febs.15272. Epub 2020 Mar 24.

Abstract

Anoikis (detachment-induced cell death) is a specific type of programmed cell death which occurs in response to the loss of the correct extracellular matrix connections. Anoikis resistance is an important mechanism in cancer invasiveness and metastatic behavior. Autophagy, on the other hand, involves the degradation of damaged organelles and the recycling of misfolded proteins and intracellular components. However, the intersection of these two cellular responses in lung cancer cells has not been extensively studied. Here, we identified that upon matrix deprivation, the lymphocyte lineage-specific Ets transcription factor SPIB was activated and directly enhanced SNAP47 transcription in certain lung cancer cells. Loss of attachment-induced autophagy significantly increased anoikis resistance by SPIB activation. Consistent with this function, SPIB depletion by short hairpin RNA abrogated SNAP47 transcriptional activation upon matrix deprivation. Therefore, these data delineate an important role of SPIB in autophagy-mediated anoikis resistance in lung cancer cells. Accordingly, these findings suggest that manipulating SPIB-regulated pathways in vivo and evaluating the impact of anoikis resistance warrant further investigation. DATABASE: RNA sequencing and ChIP sequencing data are available in Gene Expression Omnibus database under the accession numbers GSE106592 and GSE125561, respectively.

Keywords: NSCLC; SNAP47; SPIB; anoikis resistance; autophagy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Anoikis / genetics*
  • Autophagy / genetics*
  • Cell Line, Tumor
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Extracellular Matrix / metabolism
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic*
  • HEK293 Cells
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / ultrastructure
  • Lysosomes / metabolism*
  • Lysosomes / ultrastructure
  • Microscopy, Electron, Transmission
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • SNARE Proteins / genetics
  • SNARE Proteins / metabolism
  • Sequestosome-1 Protein / genetics
  • Sequestosome-1 Protein / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • DNA-Binding Proteins
  • MAP1LC3B protein, human
  • Microtubule-Associated Proteins
  • SNARE Proteins
  • SQSTM1 protein, human
  • Sequestosome-1 Protein
  • Transcription Factors
  • SPIB protein, human