ArticleNature communications2019
Kindlin-2 links mechano-environment to proline synthesis and tumor growth.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
What it found
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Who cites it
79 citing papers in PubMed, 130 citations in OpenAlex.
- Functional genomic screens uncover FERMT2 as a critical regulator of YAP/TAZ-driven tumorigenicity.Cell death and differentiation · 2026Article
- Cellular mechanometabolism: stimuli and implications.EMBO reports · 2026Review
- The Degeneration Paradox: Severely Degenerated Cervical Nucleus Pulposus Cells Display Enhanced Mechanoplasticity Under Moderate Cyclic Tensile Strain.Biomolecules · 2026Article
- Probiotic-inspired hybrid nanovesicles for enhancing immune checkpoint therapy efficiency via tumor immune microenvironment modulation.Bioactive materials · 2026Article
- Mechanical regulation of metabolism, epigenetics, and their interplay.npj biomedical innovations · 2026Review
- SureCLIP and DrCLIP: Genetic manipulation-free, generalizable interactome mapping for cells and zebrafish.bioRxiv : the preprint server for biology · 2025Article
- Proteomic insights into collagen remodeling of the calipash in Chinese soft-shelled turtle (Food chemistry. Molecular sciences · 2025Article
- The key enzyme PYCR1 in proline metabolism: a dual driver of cancer progression and fibrotic remodeling.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Emerging Roles of De Novo Proline Biosynthesis in Human Diseases.FASEB bioAdvances · 2025Review
- Proline Metabolism in Cancer: Emerging Roles in Redox Homeostasis and Therapeutic Opportunities.Cancers · 2025Review
- Pathogenesis and current status of the treatment of lung cancer associated with idiopathic pulmonary fibrosis.Respiratory research · 2025Review
- Gastrodin Alleviates Tau Pathology by Targeting the Alzheimer's Risk Gene FERMT2, Reversing the Reduction in Brain Viscoelasticity.CNS neuroscience & therapeutics · 2025Article
- Mesenchymal stromal cells promote the formation of lung cancer organoids via Kindlin-2.Stem cell research & therapy · 2025Article
- Deciphering Mitochondria: Unveiling Their Roles in Mechanosensing and Mechanotransduction.Research (Washington, D.C.) · 2025Review
- Migfilin promotes autophagic flux through direct interaction with SNAP29 and Vamp8.The Journal of cell biology · 2024Article
- Deubiquitinase USP9x regulates the proline biosynthesis pathway in non-small cell lung cancer.Cell death discovery · 2024Article
- Mechanical regulation of mitochondrial morphodynamics in cancer cells by extracellular microenvironment.Biomaterials and biosystems · 2024Article
- UHPLC-HRMS-based Multiomics to Explore the Potential Mechanisms and Biomarkers for Colorectal Cancer.BMC cancer · 2024Article
- Pan-cancer analyses suggest kindlin-associated global mechanochemical alterations.Communications biology · 2024Article
- Matrix stiffness-driven cancer progression and the targeted therapeutic strategy.Mechanobiology in medicine · 2023Review
19 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
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cell metabolism is strongly influenced by mechano-environment. We show here that a fraction of kindlin-2 localizes to mitochondria and interacts with pyrroline-5-carboxylate reductase 1 (PYCR1), a key enzyme for proline synthesis. Extracellular matrix (ECM) stiffening promotes kindlin-2 translocation into mitochondria and its interaction with PYCR1, resulting in elevation of PYCR1 level and consequent increase of proline synthesis and cell proliferation. Depletion of kindlin-2 reduces PYCR1 level, increases reactive oxygen species (ROS) production and apoptosis, and abolishes ECM stiffening-induced increase of proline synthesis and cell proliferation. In vivo, both kindlin-2 and PYCR1 levels are markedly increased in lung adenocarcinoma. Ablation of kindlin-2 in lung adenocarcinoma substantially reduces PYCR1 and proline levels, and diminishes fibrosis in vivo, resulting in marked inhibition of tumor growth and reduction of mortality rate. Our findings reveal a mechanoresponsive kindlin-2-PYCR1 complex that links mechano-environment to proline metabolism and signaling, and suggest a strategy to inhibit tumor growth.
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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.