ArticleScience advances2023
HPIP is an essential scaffolding protein running through the EGFR-RAS-ERK pathway and drives tumorigenesis.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 7 citations in OpenAlex.
- TLCD1 correlates with malignant progression of hepatocellular carcinoma and activation of the ERK signaling cascade.Scientific reports · 2026Article
- LncRNA LMCD1-AS1 Interacts with PHF8 to Promote Hepatocellular Carcinoma Resistance to Multikinase Inhibitors.International journal of biological sciences · 2026Article
- Functional loss of ERBB receptor feedback inhibitor 1 (MIG6) promotes glioblastoma tumorigenesis by aberrant activation of epidermal growth factor receptor (EGFR).Molecular oncology · 2025Article
- Clinicopathologic significance of FUT8, STX4, and calpain2 expression in ovarian cancer.American journal of translational research · 2025Article
- tRF3a-MetCAT Promotes EGFR-Targeted Therapeutic Resistance through the TRIM21-STAT1-C5a Axis in Lung Adenocarcinoma.Research (Washington, D.C.) · 2025Article
- Phosphorylation determines the glucose metabolism reprogramming and tumor-promoting activity of sine oculis homeobox 1.Signal transduction and targeted therapy · 2024Article
- Special Issue: MAPK Signaling Cascades in Human Health and Diseases.International journal of molecular sciences · 2024Article
- Navigating the ERK1/2 MAPK Cascade.Biomolecules · 2023Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The EGFR-RAS-ERK pathway plays a key role in cancer development and progression. However, the integral assembly of EGFR-RAS-ERK signaling complexes from the upstream component EGFR to the downstream component ERK is largely unknown. Here, we show that hematopoietic PBX-interacting protein (HPIP) interacts with all classical components of the EGFR-RAS-ERK pathway and forms at least two complexes with overlapping components. Experiments of HPIP knockout or knockdown and chemical inhibition of HPIP expression showed that HPIP is required for EGFR-RAS-ERK signaling complex formation, EGFR-RAS-ERK signaling activation, and EGFR-RAS-ERK signaling-mediated promotion of aerobic glycolysis as well as cancer cell growth in vitro and in vivo. HPIP expression is correlated with EGFR-RAS-ERK signaling activation and predicts worse clinical outcomes in patients with lung cancer. These results provide insights into EGFR-RAS-ERK signaling complex formation and EGFR-RAS-ERK signaling regulation and suggest that HPIP may be a promising therapeutic target for cancer with dysregulated EGFR-RAS-ERK signaling.
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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 Socratic graph.