ArticleProceedings of the National Academy of Sciences of the United States of America2020
The ABL2 kinase regulates an HSF1-dependent transcriptional program required for lung adenocarcinoma brain metastasis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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
23 citing papers in PubMed, 37 citations in OpenAlex.
- Adaptation to heat stress by diversification of the vertebrate heat shock transcription factor family.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Identification and functional validation of EPS15L1 as a key driver of triple-negative breast cancer.NPJ breast cancer · 2026Article
- FBXO31-induced ABL2 ubiquitination increases cystine-glutamate antiporter-mediated ferroptosis and inhibits malignant progression in triple-negative breast cancer.American journal of translational research · 2026Article
- Prognostic and immunological implications of protein kinases in gastric cancer: a focus on hub gene ABL2 and its impact on the polarization of M2 macrophages.Biology direct · 2025Article
- Review
- A bird's eye view of mitochondrial unfolded protein response in cancer: mechanisms, progression and further applications.Cell death & disease · 2024Review
- A ferroptosis-related signature predicts the clinical diagnosis and prognosis, and associates with the immune microenvironment of lung cancer.Discover oncology · 2024Article
- Tumor-suppressive action of miR-30a-5p in lung adenocarcinoma correlates with ABL2 inhibition and PI3K/AKT pathway inactivation.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- Overexpression of miR-532-5p restrains oxidative stress response of chondrocytes in nontraumatic osteonecrosis of the femoral head by inhibiting ABL1.Open medicine (Warsaw, Poland) · 2024Article
- Heat Shock Factor 1 Inhibition: A Novel Anti-Cancer Strategy with Promise for Precision Oncology.Cancers · 2023Review
- Single-cell RNA sequencing reveals pro-invasive cancer-associated fibroblasts in hypopharyngeal squamous cell carcinoma.Cell communication and signaling : CCS · 2023Article
- Heat shock factor 1 (HSF1) specifically potentiates c-MYC-mediated transcription independently of the canonical heat shock response.Cell reports · 2023Article
- ABL kinases regulate the stabilization of HIF-1α and MYC through CPSF1.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Involvement of redox signalling in tumour cell dormancy and metastasis.Cancer metastasis reviews · 2023Review
- ABL1/2 and DDR1 Drive MEKi Resistance in NRAS-Mutant Melanomas by Stabilizing RAF/MYC/ETS1 and Promoting RAF Homodimerization.Cancers · 2023Article
- Targeting HSF1 for cancer treatment: mechanisms and inhibitor development.Theranostics · 2023Review
- Integrated analysis of single-cell and Bulk RNA sequencing reveals a malignancy-related signature in lung adenocarcinoma.Frontiers in oncology · 2023Article
- HSF1 facilitates the multistep process of lymphatic metastasis in bladder cancer via a novel PRMT5-WDR5-dependent transcriptional program.Cancer communications (London, England) · 2022Article
- Heat Shock Proteins and HSF1 in Cancer.Frontiers in oncology · 2022Review
- ABL allosteric inhibitors synergize with statins to enhance apoptosis of metastatic lung cancer cells.Cell reports · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Brain metastases are the most common intracranial tumors in adults and are associated with increased patient morbidity and mortality. Limited therapeutic options are currently available for the treatment of brain metastasis. Here, we report on the discovery of an actionable signaling pathway utilized by metastatic tumor cells whereby the transcriptional regulator Heat Shock Factor 1 (HSF1) drives a transcriptional program, divergent from its canonical role as the master regulator of the heat shock response, leading to enhanced expression of a subset of E2F transcription factor family gene targets. We find that HSF1 is required for survival and outgrowth by metastatic lung cancer cells in the brain parenchyma. Further, we identify the ABL2 tyrosine kinase as an upstream regulator of HSF1 protein expression and show that the Src-homology 3 (SH3) domain of ABL2 directly interacts with HSF1 protein at a noncanonical, proline-independent SH3 interaction motif. Pharmacologic inhibition of the ABL2 kinase using small molecule allosteric inhibitors, but not ATP-competitive inhibitors, disrupts this interaction. Importantly, knockdown as well as pharmacologic inhibition of ABL2 using allosteric inhibitors impairs expression of HSF1 protein and HSF1-E2F transcriptional gene targets. Collectively, these findings reveal a targetable ABL2-HSF1-E2F signaling pathway required for survival by brain-metastatic tumor cells.
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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.