Evidence map›Paper›PMID 40721523›Full record

ArticleBritish journal of cancer2025

Enhanced HER2 internalization by clathrin-dependent endocytosis in non-small cell lung cancer positive for HER2 mutations.

Atsushi Shimauchi, Eiji Iwama, Ritsu Ibusuki, Hirono Tsutsumi, Daisuke Shibahara, Kohei Otsubo, Yasuto Yoneshima, Kentaro Tanaka, Isamu Okamoto

Abstract read
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In one paragraph

Article in British journal of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Atsushi ShimauchiDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Eiji IwamaDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. iwama.eiji.800@m.kyushu-u.ac.jp.ORCID http://orcid.org/0000-0001-8252-290X
Ritsu IbusukiDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Hirono TsutsumiDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Daisuke ShibaharaDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Kohei OtsuboDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Yasuto YoneshimaDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Kentaro TanakaDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Isamu OkamotoDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Funding

MEXT | Japan Society for the Promotion of Science (JSPS) JP24K11345
6 · The paper itself

Abstract

backgroundHER2-targeted antibody-drug conjugates (ADCs) have shown marked efficacy for HER2 mutation-positive non-small cell lung cancer (NSCLC). The intracellular trafficking of mutant HER2 has remained to be fully elucidated, however.

methodsHER2 dynamics were examined in cells expressing wild-type (WT) or mutant HER2 with the use of live cell imaging and an in situ proximity ligation assay. Proteins related to mutant HER2 trafficking were identified by liquid chromatography and tandem mass spectrometry.

resultsHER2 internalization was enhanced in NSCLC cells expressing mutant HER2 compared with those expressing HER2(WT). Homodimers of HER2(WT) were localized mainly at the cell surface, whereas those of mutant HER2 were present mostly in the cytoplasm. Knockdown of EGFR or HER3 suppressed internalization of HER2(WT) but not that of mutant HER2. The enhanced internalization of mutant HER2 was mediated by clathrin-dependent endocytosis, as was reflected by increased binding of the ubiquitin ligase c-Cbl to mutant HER2 and its consequent ubiquitination, and was attenuated by treatment with zongertinib, a HER2-specific tyrosine kinase inhibitor.

conclusionsUpregulation of HER2 phosphorylation promotes internalization of mutant HER2 mediated by clathrin-dependent endocytosis, likely contributing to the efficacy of HER2-targeted ADCs in NSCLC positive for HER2 mutations.

Indexed as

Carcinoma, Non-Small-Cell LungClathrinEndocytosisErb-b2 Receptor Tyrosine KinasesLung NeoplasmsCell Line, TumorHumansMutationProtein TransportProto-Oncogene Proteins c-cblUbiquitinationClathrinERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesProto-Oncogene Proteins c-cbl

Identifiers

PMID40721523
PMCPMC12479963

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