ArticleOncogene2021
A SNAI2-PEAK1-INHBA stromal axis drives progression and lapatinib resistance in HER2-positive breast cancer by supporting subpopulations of tumor cells positive for antiapoptotic and stress signaling markers.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- JAK-STAT signaling pathway in cancer: from molecular mechanisms to clinical intervention.Molecular cancer · 2026Review
- PEAK1 promotes prostate cancer progression and docetaxel resistance by mediating the polarization of tumor-associated macrophages.European journal of medical research · 2026Article
- Activin A-Targeted Therapy in Cancer: An Updated Review on Challenges and Opportunities in Clinical Translation.Current pharmaceutical design · 2026Review
- INHBA promotes chemoresistance in pancreatic cancer by enhancing CTPS1 stability and mediating pyrimidine metabolism.Cancer cell international · 2025Article
- Pan-cancer analysis of INHBA indicates its potential prognostic value and correlation with HNSC and LIHC.Discover oncology · 2025Article
- The role of genetics and epigenetics in breast cancer: A comprehensive review of metastasis, risk factors, and future perspectives.Journal of pharmaceutical analysis · 2025Review
- Activin A Secreted by Cancer-Associated Fibroblasts Reduces the Sensitivity of Breast Cancer Cells to Ixazomib via Inhibition of Proteasome Activity.Biomolecules · 2025Article
- PEAK1 maintains tight junctions in intestinal epithelial cells and resists colitis by inhibiting autophagy-mediated ZO-1 degradation.Nature communications · 2025Article
- Tumor-associated mesenchymal stem/stromal cells in tumor microenvironment and carcinogenesis.Experimental hematology & oncology · 2025Review
- Current understanding of PEAK family members in regulation of cellular signaling pathways and cancer therapy.Molecular and cellular biochemistry · 2025Review
- INHBABMC cancer · 2025Article
- Review
- Colorectal carcinoma progression is not influenced by the pseudokinase PEAK1.Scientific reports · 2024Article
- Rational Design of HER2-Targeted Combination Therapies to Reverse Drug Resistance in Fibroblast-Protected HER2+ Breast Cancer Cells.Cellular and molecular bioengineering · 2024Article
- The complex interplay of tumor-infiltrating cells in driving therapeutic resistance pathways.Cell communication and signaling : CCS · 2024Review
- Comprehensively prognostic and immunological analysis of snail family transcriptional repressor 2 in pan-cancer and identification in pancreatic carcinoma.Frontiers in immunology · 2023Article
- The value of cuproptosis-related differential genes in guiding prognosis and immune status in patients with skin cutaneous melanoma.Frontiers in pharmacology · 2023Article
- BMSCs overexpressed ISL1 reduces the apoptosis of islet cells through ANLN carrying exosome, INHBA, and caffeine.Cellular and molecular life sciences : CMLS · 2022Article
- Fate decisions of breast cancer stem cells in cancer progression.Frontiers in oncology · 2022Review
- Single-cell landscape reveals active cell subtypes and their interaction in the tumor microenvironment of gastric cancer.Theranostics · 2022Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
Intercellular mechanisms by which the stromal microenvironment contributes to solid tumor progression and targeted therapy resistance remain poorly understood, presenting significant clinical hurdles. PEAK1 (Pseudopodium-Enriched Atypical Kinase One) is an actin cytoskeleton- and focal adhesion-associated pseudokinase that promotes cell state plasticity and cancer metastasis by mediating growth factor-integrin signaling crosstalk. Here, we determined that stromal PEAK1 expression predicts poor outcomes in HER2-positive breast cancers high in SNAI2 expression and enriched for MSC content. Specifically, we identified that the fibroblastic stroma in HER2-positive breast cancer patient tissue stains positive for both nuclear SNAI2 and cytoplasmic PEAK1. Furthermore, mesenchymal stem cells (MSCs) and cancer-associated fibroblasts (CAFs) express high PEAK1 protein levels and potentiate tumorigenesis, lapatinib resistance and metastasis of HER2-positive breast cancer cells in a PEAK1-dependent manner. Analysis of PEAK1-dependent secreted factors from MSCs revealed INHBA/activin-A as a necessary factor in the conditioned media of PEAK1-expressing MSCs that promotes lapatinib resistance. Single-cell CycIF analysis of MSC-breast cancer cell co-cultures identified enrichment of p-Akt
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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 OpenQuestion graph.