ArticleCellular and molecular life sciences : CMLS2019
HIF-1α-derived cell-penetrating peptides inhibit ERK-dependent activation of HIF-1 and trigger apoptosis of cancer cells under hypoxia.
Article in Cellular and molecular life sciences : CMLS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses that pooled 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.
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
33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 47 citations in OpenAlex.
- TRP Channels Interactome as a Novel Therapeutic Target in Breast Cancer.Frontiers in oncology · 2021Pooled it
- Prognostic and Clinicopathological Significance of Hypoxia-Inducible Factor-1α in Endometrial Cancer: A Meta-Analysis.Frontiers in oncology · 2020Pooled it
- HIF inhibition: Current strategies and clinical challenges.Redox biology · 2026Review
- Octacosanol Suppresses Lung Cancer Metastasis and Angiogenesis via Targeting MMPs and VEGF.Cells · 2026Article
- Exploring CPP Enhanced Hypoxia Targeting: An Approach Using Radiolabeled 2-nitroimidazole TAT Conjugate.Drug development research · 2026Article
- Targeting the ERK1/2 and p38 MAPK pathways attenuates Golgi tethering factor golgin-97 depletion-induced cancer progression in breast cancer.Cell communication and signaling : CCS · 2025Article
- An immunotherapeutic hydrogel booster inhibits tumor recurrence and promotes wound healing for postoperative management of melanoma.Bioactive materials · 2024Article
- Advances in peptide-based drug delivery systems.Heliyon · 2024Review
- Combinatorial regulation by ERK1/2 and CK1δ protein kinases leads to HIF-1α association with microtubules and facilitates its symmetrical distribution during mitosis.Cellular and molecular life sciences : CMLS · 2024Article
- Sevoflurane but not propofol enhances ovarian cancer cell biology through regulating cellular metabolic and signaling mechanisms.Cell biology and toxicology · 2023Article
- Pathophysiological mechanisms and therapeutic approaches in obstructive sleep apnea syndrome.Signal transduction and targeted therapy · 2023Review
- Morroniside inhibits Beclin1-dependent autophagic death and Bax-dependent apoptosis in cardiomyocytes through repressing BCL2 phosphorylation.In vitro cellular & developmental biology. Animal · 2023Article
- Review
- NF-κB mediated regulation of tumor cell proliferation in hypoxic microenvironment.Frontiers in pharmacology · 2023Review
- The role of cell-penetrating peptides in potential anti-cancer therapy.Clinical and translational medicine · 2022Review
- Investigating the role of peptides in effective therapies against cancer.Cancer cell international · 2022Review
- [Co-Culturing of Osteoblasts and Chondrocytes Upregulates HIF-1 Pathway of Chondrocytes via MAPK Signaling].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2022Article
- ERK signaling controls productive HIF-1 binding to chromatin and cancer cell adaptation to hypoxia through HIF-1α interaction with NPM1.Molecular oncology · 2021Article
- TAT for Enzyme/Protein Delivery to Restore or Destroy Cell Activity in Human Diseases.Life (Basel, Switzerland) · 2021Review
- Delivery of Various Cargos into Cancer Cells and Tissues via Cell-Penetrating Peptides: A Review of the Last Decade.Pharmaceutics · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
Hypoxia is frequently encountered in the microenvironment of solid tumors. Hypoxia-inducible factors (HIFs), the main effectors of cell response to hypoxia, promote cancer cell survival and progression. HIF-1α, the oxygen-regulated subunit of HIF-1, is often correlated with oncogenesis and represents an attractive therapeutic target. We have previously reported that activation HIF-1α by ERK involves modification of two serine residues and masking of a nuclear export signal (NES), all inside a 43-amino acid domain termed ERK Targeted Domain (ETD). Overexpression of ETD variants including wild-type, phospho-mimetic (SE) or NES-less (IA) mutant forms caused HIF-1 inactivation in two hepatocarcinoma cell lines, while a phospho-deficient (SA) form was ineffective and acted as a sequence-specific negative control. To deliver these ETD forms directly into cancer cells, they were fused to the HIV TAT-sequence and produced as cell-permeable peptides. When the TAT-ETD peptides were added to the culture medium of Huh7 cells, they entered the cells and, with the exception of ETD-SA, accumulated inside the nucleus, caused mislocalization of endogenous HIF-1α to the cytoplasm, significant reduction of HIF-1 activity and inhibition of expression of specific HIF-1, but not HIF-2, gene targets under hypoxia. More importantly, transduced nuclear TAT-ETD peptides restricted migration, impaired colony formation and triggered apoptotic cell death of cancer cells grown under hypoxia, while they produced no effects in normoxic cells. These data demonstrate the importance of ERK-mediated activation of HIF-1 for low oxygen adaptation and the applicability of ETD peptide derivatives as sequence-specific HIF-1 and cancer cell growth inhibitors under hypoxia.
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.