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.
journal_name
Dev Celljournal_title
Developmental cellauthors
Chen PH,Bendris N,Hsiao YJ,Reis CR,Mettlen M,Chen HY,Yu SL,Schmid SLdoi
10.1016/j.devcel.2017.01.007subject
Has Abstractpub_date
2017-02-06 00:00:00pages
278-288.e5issue
3eissn
1534-5807issn
1878-1551pii
S1534-5807(17)30007-2journal_volume
40pub_type
杂志文章abstract：:Cell competition promotes the elimination of weaker cells from a growing population. Here we investigate how cells of Drosophila wing imaginal discs distinguish "winners" from "losers" during cell competition. Using genomic and functional assays, we have identified several factors implicated in the process, including ...
journal_title：Developmental cell
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journal_title：Developmental cell
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journal_title：Developmental cell
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journal_title：Developmental cell
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journal_title：Developmental cell
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