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

20 Citations (Scopus)

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

Fingerprint

Dynamin I
Clathrin
Crosstalk
Endocytosis
Epidermal Growth Factor Receptor
Neoplasm Metastasis
Non-Small Cell Lung Carcinoma
Cells
Clathrin Light Chains
Phosphorylation
Epidermal Growth Factor
Machinery
Cell Movement
Neoplasms
Protein Isoforms
Up-Regulation
Chemical activation
Feedback

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

Cite this

Crosstalk between CLCb/Dyn1-Mediated Adaptive Clathrin-Mediated Endocytosis and Epidermal Growth Factor Receptor Signaling Increases Metastasis. / Chen, Ping Hung; Bendris, Nawal; Hsiao, Yi Jing; Reis, Carlos R.; Mettlen, Marcel; Chen, Hsuan Yu; Yu, Sung Liang; Schmid, Sandra L.

In: Developmental Cell, Vol. 40, No. 3, 06.02.2017, p. 278-288.e5.

Research output: Contribution to journalArticle

Chen, Ping Hung ; Bendris, Nawal ; Hsiao, Yi Jing ; Reis, Carlos R. ; Mettlen, Marcel ; Chen, Hsuan Yu ; Yu, Sung Liang ; Schmid, Sandra L. / Crosstalk between CLCb/Dyn1-Mediated Adaptive Clathrin-Mediated Endocytosis and Epidermal Growth Factor Receptor Signaling Increases Metastasis. In: Developmental Cell. 2017 ; Vol. 40, No. 3. pp. 278-288.e5.
@article{eacf2835303e45e3ad94572d1a8edfdb,
title = "Crosstalk between CLCb/Dyn1-Mediated Adaptive Clathrin-Mediated Endocytosis and Epidermal Growth Factor Receptor Signaling Increases Metastasis",
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.",
keywords = "Akt/GSK3β signaling, cell migration, clathrin light chain, clathrin-mediated endocytosis, dynamin-1, metastasis, non-small-cell lung cancer (NSCLC), receptor recycling",
author = "Chen, {Ping Hung} and Nawal Bendris and Hsiao, {Yi Jing} and Reis, {Carlos R.} and Marcel Mettlen and Chen, {Hsuan Yu} and Yu, {Sung Liang} and Schmid, {Sandra L.}",
year = "2017",
month = "2",
day = "6",
doi = "10.1016/j.devcel.2017.01.007",
language = "English (US)",
volume = "40",
pages = "278--288.e5",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "3",

}

TY - JOUR

T1 - Crosstalk between CLCb/Dyn1-Mediated Adaptive Clathrin-Mediated Endocytosis and Epidermal Growth Factor Receptor Signaling Increases Metastasis

AU - Chen, Ping Hung

AU - Bendris, Nawal

AU - Hsiao, Yi Jing

AU - Reis, Carlos R.

AU - Mettlen, Marcel

AU - Chen, Hsuan Yu

AU - Yu, Sung Liang

AU - Schmid, Sandra L.

PY - 2017/2/6

Y1 - 2017/2/6

N2 - 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.

AB - 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.

KW - Akt/GSK3β signaling

KW - cell migration

KW - clathrin light chain

KW - clathrin-mediated endocytosis

KW - dynamin-1

KW - metastasis

KW - non-small-cell lung cancer (NSCLC)

KW - receptor recycling

UR - http://www.scopus.com/inward/record.url?scp=85011591424&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85011591424&partnerID=8YFLogxK

U2 - 10.1016/j.devcel.2017.01.007

DO - 10.1016/j.devcel.2017.01.007

M3 - Article

VL - 40

SP - 278-288.e5

JO - Developmental Cell

JF - Developmental Cell

SN - 1534-5807

IS - 3

ER -