Crosstalk between CLCb/Dyn1-Mediated Adaptive Clathrin-Mediated Endocytosis and Epidermal Growth Factor Receptor Signaling Increases Metastasis

Ping Hung Chen, Nawal Bendris, Yi Jing Hsiao, Carlos R. Reis, Marcel Mettlen, Hsuan Yu Chen, Sung Liang Yu, Sandra L. Schmid

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Signaling receptors are internalized and regulated by clathrin-mediated endocytosis (CME). Two clathrin light chain isoforms, CLCa and CLCb, are integral components of the endocytic machinery whose differential functions remain unknown. We report that CLCb is specifically upregulated in non-small-cell lung cancer (NSCLC) cells and is associated with poor patient prognosis. Engineered single CLCb-expressing NSCLC cells, as well as “switched” cells that predominantly express CLCb, exhibit increased rates of CME and altered clathrin-coated pit dynamics. This “adaptive CME” resulted from upregulation of dynamin-1 (Dyn1) and its activation through a positive feedback loop involving enhanced epidermal growth factor (EGF)-dependent Akt/GSK3β phosphorylation. CLCb/Dyn1-dependent adaptive CME selectively altered EGF receptor trafficking, enhanced cell migration in vitro, and increased the metastatic efficiency of NSCLC cells in vivo. We define molecular mechanisms for adaptive CME in cancer cells and a role for the reciprocal crosstalk between signaling and CME in cancer progression.

Original languageEnglish (US)
Pages (from-to)278-288.e5
JournalDevelopmental Cell
Volume40
Issue number3
DOIs
StatePublished - Feb 6 2017

Keywords

  • Akt/GSK3β signaling
  • cell migration
  • clathrin light chain
  • clathrin-mediated endocytosis
  • dynamin-1
  • metastasis
  • non-small-cell lung cancer (NSCLC)
  • receptor recycling

ASJC Scopus subject areas

  • Developmental Biology

Fingerprint Dive into the research topics of 'Crosstalk between CLCb/Dyn1-Mediated Adaptive Clathrin-Mediated Endocytosis and Epidermal Growth Factor Receptor Signaling Increases Metastasis'. Together they form a unique fingerprint.

  • Cite this