ArticleThe EMBO journal2015
LAPTM4B is a PtdIns(4,5)P2 effector that regulates EGFR signaling, lysosomal sorting, and degradation.
Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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.
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.
Who cites it
63 citing papers in PubMed, 87 citations in OpenAlex.
- PAX9 activates autophagy through a transcription-dependent mechanism, promoting EGFR degradation to restrict cell survival in oral cancer.British journal of cancer · 2026Article
- Inhibition of autophagy increases head and neck cancer sensitivity to cetuximab and radiation therapy.Scientific reports · 2026Article
- Beyond the membrane: rethinking EGFR signaling in physiology and cancer.Cellular and molecular life sciences : CMLS · 2026Review
- LAPTM proteins in neurological disorders - Autophagy-lysosome dysfunction and therapeutic targets: A review.Biomolecules & biomedicine · 2026Review
- LAPTM4B Confers Resistance to EGFR-TKIs by Suppressing the Proteasomal Degradation of ATP1A1 in Non-small Cell Lung Cancer.International journal of biological sciences · 2026Article
- The Biological Role and Clinical Significance of BECLIN-1 in Cancer.International journal of molecular sciences · 2025Review
- A CMTM6 Nanobody Overcomes EGFR-TKI Resistance in Non-Small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- LAPTM4B enhances the stemness of CD133JHEP reports : innovation in hepatology · 2025Article
- SNX5 promotes antigen presentation in B cells by dual regulation of actin and lysosomal dynamics.Life science alliance · 2025Article
- The role and regulatory mechanism of lysosome associated protein transmembrane 4β in tumors.Frontiers in oncology · 2025Review
- Hepatitis B virus entry, assembly, and egress.Microbiology and molecular biology reviews : MMBR · 2024Review
- LAPTM4B counteracts ferroptosis via suppressing the ubiquitin-proteasome degradation of SLC7A11 in non-small cell lung cancer.Cell death & disease · 2024Article
- Nuclear phosphoinositide signaling promotes YAP/TAZ-TEAD transcriptional activity in breast cancer.The EMBO journal · 2024Article
- Environmental pollutants and phosphoinositide signaling in autoimmunity.Journal of hazardous materials · 2024Review
- Phosphoglycerate kinase 1 acts as a cargo adaptor to promote EGFR transport to the lysosome.Nature communications · 2024Article
- Endosomal Arl4A attenuates EGFR degradation by binding to the ESCRT-II component VPS36.Nature communications · 2023Article
- Review
- LAPTM4B-YAP loop feedback amplification enhances the stemness of hepatocellular carcinoma.iScience · 2023Article
- miR-137-LAPTM4B regulates cytoskeleton organization and cancer metastasis via the RhoA-LIMK-Cofilin pathway in osteosarcoma.Oncogenesis · 2023Article
- Aspartate β-Hydroxylase Serves as a Prognostic Biomarker for Neoadjuvant Chemotherapy in Gastric Cancer.International journal of molecular sciences · 2023Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Lysosomal degradation is essential for the termination of EGF-stimulated EGF receptor (EGFR) signaling. This requires EGFR sorting to the intraluminal vesicles (ILVs) of multi-vesicular endosomes (MVEs). Cytosolic proteins including the ESCRT machineries are key regulators of EGFR intraluminal sorting, but roles for endosomal transmembrane proteins in receptor sorting are poorly defined. Here, we show that LAPTM4B, an endosomal transmembrane oncoprotein, inhibits EGF-induced EGFR intraluminal sorting and lysosomal degradation, leading to enhanced and prolonged EGFR signaling. LAPTM4B blocks EGFR sorting by promoting ubiquitination of Hrs (an ESCRT-0 subunit), which inhibits the Hrs association with ubiquitinated EGFR. This is counteracted by the endosomal PIP kinase, PIPKIγi5, which directly binds LAPTM4B and neutralizes the inhibitory function of LAPTM4B in EGFR sorting by generating PtdIns(4,5)P2 and recruiting SNX5. PtdIns(4,5)P2 and SNX5 function together to protect Hrs from ubiquitination, thereby promoting EGFR intraluminal sorting. These results reveal an essential layer of EGFR trafficking regulated by LAPTM4B, PtdIns(4,5)P2 signaling, and the ESCRT complex and define a mechanism by which the oncoprotein LAPTM4B can transform cells and promote tumor progression.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.