ArticleCancer research2019
Targeting Mechanoresponsive Proteins in Pancreatic Cancer: 4-Hydroxyacetophenone Blocks Dissemination and Invasion by Activating MYH14.
Article in Cancer research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 84 citations in OpenAlex.
- The ESR1-MYH14 axis functions as a critical driver of cervical cancer progression and metastasis.Translational oncology · 2026Article
- Deformability screening identifies NUDT5 as a mediator of cellular mechanobiology.bioRxiv : the preprint server for biology · 2026Article
- Article
- Cellular elasticity drives mechano-adaptation against fluid shear stress.Journal of cell science · 2025Article
- Complementary cytoskeletal feedback loops control signal transduction excitability and cell polarity.Nature communications · 2025Article
- Ras-mediated dynamic and biphasic regulation of cell migration.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Characteristics of gut microbiota and metabolites in extrahepatic cholangiocarcinoma and their prognostic value for resectable lesions.Frontiers in cellular and infection microbiology · 2025Article
- Compressive stresses in cancer: characterization and implications for tumour progression and treatment.Nature reviews. Cancer · 2024Review
- Prognostic and therapeutic implications of tumor-restrictive type III collagen in the breast cancer microenvironment.NPJ breast cancer · 2024Article
- Identification and Validation of Tumor Microenvironment-Associated Signature in Clear-Cell Renal Cell Carcinoma through Integration of DNA Methylation and Gene Expression.International journal of molecular sciences · 2024Article
- Structure, regulation, and mechanisms of nonmuscle myosin-2.Cellular and molecular life sciences : CMLS · 2024Review
- Sesamolin serves as an MYH14 inhibitor to sensitize endometrial cancer to chemotherapy and endocrine therapy via suppressing MYH9/GSK3β/β-catenin signaling.Cellular & molecular biology letters · 2024Article
- Cancer cell response to extrinsic and intrinsic mechanical cue: opportunities for tumor apoptosis strategies.Regenerative biomaterials · 2024Review
- Expression of nonmuscle myosin IIC is regulated by non-canonical binding activity of miRNAs.iScience · 2023Article
- MYH10 activation rescues contractile defects in arrhythmogenic cardiomyopathy (ACM).Nature communications · 2023Article
- Targeting MYH9 represses USP14-mediated NAP1L1 deubiquitination and cell proliferation in glioma.Cancer cell international · 2023Article
- Article
- A biomechanical view of epigenetic tumor regulation.Journal of biological physics · 2023Review
- Nonmuscle myosin IIB is a driver of cellular reprogramming.Molecular biology of the cell · 2023Article
- MYH10 Combines with MYH9 to Recruit USP45 by Deubiquitinating Snail and Promotes Serous Ovarian Cancer Carcinogenesis, Progression, and Cisplatin Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
Metastasis is complex, involving multiple genetic, epigenetic, biochemical, and physical changes in the cancer cell and its microenvironment. Cells with metastatic potential are often characterized by altered cellular contractility and deformability, lending them the flexibility to disseminate and navigate through different microenvironments. We demonstrate that mechanoresponsiveness is a hallmark of pancreatic cancer cells. Key mechanoresponsive proteins, those that accumulate in response to mechanical stress, specifically nonmuscle myosin IIA (MYH9) and IIC (MYH14), α-actinin 4, and filamin B, were highly expressed in pancreatic cancer as compared with healthy ductal epithelia. Their less responsive sister paralogs-myosin IIB (MYH10), α-actinin 1, and filamin A-had lower expression differential or disappeared with cancer progression. We demonstrate that proteins whose cellular contributions are often overlooked because of their low abundance can have profound impact on cell architecture, behavior, and mechanics. Here, the low abundant protein MYH14 promoted metastatic behavior and could be exploited with 4-hydroxyacetophenone (4-HAP), which increased MYH14 assembly, stiffening cells. As a result, 4-HAP decreased dissemination, induced cortical actin belts in spheroids, and slowed retrograde actin flow. 4-HAP also reduced liver metastases in human pancreatic cancer-bearing nude mice. Thus, increasing MYH14 assembly overwhelms the ability of cells to polarize and invade, suggesting targeting the mechanoresponsive proteins of the actin cytoskeleton as a new strategy to improve the survival of patients with pancreatic cancer. SIGNIFICANCE: This study demonstrates that mechanoresponsive proteins become upregulated with pancreatic cancer progression and that this system of proteins can be pharmacologically targeted to inhibit the metastatic potential of pancreatic cancer cells.
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Registered trials
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