Gradient Rotating Magnetic Fields Impairing F-Actin-Related Gene CCDC150 to Inhibit Triple-Negative Breast Cancer Metastasis by Inactivating TGF-β1/SMAD3 Signaling Pathway

Triple-negative breast cancer (TNBC) is the most aggressive and lethal malignancy in women, with a lack of effective targeted drugs and treatment techniques. Gradient rotating magnetic field (RMF) is a new technology used in oncology physiotherapy, showing promising clinical applications due to its satisfactory biosafety and the abundant mechanical force stimuli it provides. However, its antitumor effects and underlying molecular mechanisms are not yet clear. We designed two sets of gradient RMF devices for cell culture and animal handling. Gradient RMF exposure had a notable impact on the F-actin arrangement of MDA-MB-231, BT-549, and MDA-MB-468 cells, inhibiting cell migration and invasion. A potential cytoskeleton F-actin-associated gene, CCDC150, was found to be enriched in clinical TNBC tumors and cells. CCDC150 negatively correlated with the overall survival rate of TNBC patients. CCDC150 promoted TNBC migration and invasion via activation of the transforming growth factor β1 (TGF-β1)/SMAD3 signaling pathway in vitro and in vivo. CCDC150 was also identified as a magnetic field response gene, and it was marked down-regulated after gradient RMF exposure. CCDC150 silencing and gradient RMF exposure both suppressed TNBC tumor growth and liver metastasis. Therefore, gradient RMF exposure may be an effective TNBC treatment, and CCDC150 may emerge as a potential target for TNBC therapy.

[1]  W. Fang,et al.  Regulatory network and targeted interventions for CCDC family in tumor pathogenesis. , 2023, Cancer letters.

[2]  P. Shang,et al.  Magnetic Fields Reduce Apoptosis by Suppressing Phase Separation of Tau-441 , 2023, Research.

[3]  Ge Zhang,et al.  The effect of magnetic fields on tumor occurrence and progression: Recent advances. , 2023, Progress in biophysics and molecular biology.

[4]  Yang Sun,et al.  Rotating Magnetic Field Mitigates Ankylosing Spondylitis Targeting Osteocytes and Chondrocytes via Ameliorating Immune Dysfunctions , 2023, Cells.

[5]  Yongsen Zhang,et al.  Intermittent F-actin Perturbations by Magnetic Fields Inhibit Breast Cancer Metastasis , 2023, Research.

[6]  Tinghong Ye,et al.  An oral phenylacrylic acid derivative suppressed hepatic stellate cell activation and ameliorated liver fibrosis by blocking TGF‐β1 signalling , 2022, Liver international : official journal of the International Association for the Study of the Liver.

[7]  Gang Zhao,et al.  Exosomes deliver lncRNA DARS-AS1 siRNA to inhibit chronic unpredictable mild stress-induced TNBC metastasis. , 2022, Cancer letters.

[8]  Ying Zhang,et al.  Multifunctional nanosystems sequentially regulating intratumor Fenton chemistry by remodeling the tumor microenvironment to reinforce chemodynamic therapy. , 2022, Biomaterials advances.

[9]  Junfeng Zhang,et al.  Sox9/CXCL5 axis facilitates tumour cell growth and invasion in hepatocellular carcinoma , 2022, The FEBS journal.

[10]  M. Durante,et al.  A Combination of Cabozantinib and Radiation Does Not Lead to an Improved Growth Control of Tumors in a Preclinical 4T1 Breast Cancer Model , 2021, Frontiers in Oncology.

[11]  L. Bouwens,et al.  Transcutaneous Vagal Nerve Stimulation Alone or in Combination With Radiotherapy Stimulates Lung Tumor Infiltrating Lymphocytes But Fails to Suppress Tumor Growth , 2021, Frontiers in Immunology.

[12]  U. Tazebay,et al.  Coiled-coil domain-containing protein-124 (Ccdc124) is a novel RNA binding factor up-regulated in endometrial, ovarian, and urinary bladder cancers. , 2021, Cancer biomarkers : section A of Disease markers.

[13]  P. Shang,et al.  Magnetic fields as a potential therapy for diabetic wounds based on animal experiments and clinical trials , 2021, Cell proliferation.

[14]  A. Jemal,et al.  Cancer Statistics, 2021 , 2021, CA: a cancer journal for clinicians.

[15]  Afsaneh Mojra,et al.  Numerical analysis of non-Fourier thermal response of lung tissue based on experimental data with application in laser therapy , 2020, Comput. Methods Programs Biomed..

[16]  E. Yang,et al.  An open-label, pilot study of veliparib and lapatinib in patients with metastatic, triple-negative breast cancer , 2020, Breast cancer research : BCR.

[17]  E. Song,et al.  DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25 , 2020, Nature.

[18]  M. Cristofanilli,et al.  The Landscape of Targeted Therapies in TNBC , 2020, Cancers.

[19]  M. Gao,et al.  Low‐Frequency Magnetic Field of Appropriate Strengths Changed Secondary Metabolite Production and Na+ Concentration of Intracellular and Extracellular Monascus purpureus , 2020, Bioelectromagnetics.

[20]  J. Friend,et al.  Pulsed Low-Frequency Magnetic Fields Induce Tumor Membrane Disruption and Altered Cell Viability , 2020, Biophysical journal.

[21]  L. Jie,et al.  Recent treatment progress of triple negative breast cancer. , 2019, Progress in biophysics and molecular biology.

[22]  Xin Zhang,et al.  Effects of 3.5–23.0 T static magnetic fields on mice: A safety study , 2019, NeuroImage.

[23]  Wendy S. Beane,et al.  Weak magnetic fields alter stem cell–mediated growth , 2019, Science Advances.

[24]  I. Matsuura,et al.  Impaired mammary tumor formation and metastasis by the point mutation of a Smad3 linker phosphorylation site. , 2018, Biochimica et biophysica acta. Molecular basis of disease.

[25]  D. Yin,et al.  A periodic magnetic field as a special environment for scientific research created by rotating permanent magnet pairs. , 2018, The Review of scientific instruments.

[26]  Jun Yu Li,et al.  Moderate intensity low frequency rotating magnetic field inhibits breast cancer growth in mice , 2018, Electromagnetic biology and medicine.

[27]  Jordan M. Fletcher,et al.  De novo coiled-coil peptides as scaffolds for disrupting protein–protein interactions† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c8sc02643b , 2018, Chemical science.

[28]  A. Dejneka,et al.  Cells in the Non‐Uniform Magnetic World: How Cells Respond to High‐Gradient Magnetic Fields , 2018, BioEssays : news and reviews in molecular, cellular and developmental biology.

[29]  C. Zhang,et al.  SHCBP1 promotes synovial sarcoma cell metastasis via targeting TGF-β1/Smad signaling pathway and is associated with poor prognosis , 2017, Journal of Experimental & Clinical Cancer Research.

[30]  Huizhen Wang,et al.  Magnetic Fields and Reactive Oxygen Species , 2017, International journal of molecular sciences.

[31]  Yuquan Wei,et al.  Human Adipose‐Derived Mesenchymal Stem Cell‐Secreted CXCL1 and CXCL8 Facilitate Breast Tumor Growth By Promoting Angiogenesis , 2017, Stem cells.

[32]  Laising Yen,et al.  Noncoding Effects of Circular RNA CCDC66 Promote Colon Cancer Growth and Metastasis. , 2017, Cancer research.

[33]  M. Mauter,et al.  Computing the Diamagnetic Susceptibility and Diamagnetic Anisotropy of Membrane Proteins from Structural Subunits. , 2017, Journal of chemical theory and computation.

[34]  Jiayi Chen,et al.  Post-operative radiotherapy is beneficial for T1/T2 triple negative breast cancer patients with four or more positive lymph nodes , 2017, Oncotarget.

[35]  L. Ding,et al.  LF-MF inhibits iron metabolism and suppresses lung cancer through activation of P53-miR-34a-E2F1/E2F3 pathway , 2017, Scientific Reports.

[36]  T. Mitchison,et al.  27 T ultra-high static magnetic field changes orientation and morphology of mitotic spindles in human cells , 2017, eLife.

[37]  A. Lupas,et al.  The Structure and Topology of α-Helical Coiled Coils , 2017, Sub-cellular biochemistry.

[38]  A. Dejneka,et al.  How a High-Gradient Magnetic Field Could Affect Cell Life , 2016, Scientific Reports.

[39]  A. Rapoport,et al.  New strategies for the treatment and prevention of primary headache disorders , 2016, Nature Reviews Neurology.

[40]  Guanglong Jiang,et al.  Comprehensive comparison of molecular portraits between cell lines and tumors in breast cancer , 2016, BMC Genomics.

[41]  Qingsong Liu,et al.  Moderate and strong static magnetic fields directly affect EGFR kinase domain orientation to inhibit cancer cell proliferation , 2016, Oncotarget.

[42]  Mingjian Ding,et al.  Association between transforming growth factor-β1 expression and the clinical features of triple negative breast cancer. , 2016, Oncology letters.

[43]  L. Vargas-Roig,et al.  Hyperthermia effects on Hsp27 and Hsp72 associations with mismatch repair (MMR) proteins and cisplatin toxicity in MMR-deficient/proficient colon cancer cell lines , 2015, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[44]  Z. Tulassay,et al.  Influence of inhomogeneous static magnetic field-exposure on patients with erosive gastritis: a randomized, self- and placebo-controlled, double-blind, single centre, pilot study , 2014, Journal of The Royal Society Interface.

[45]  Bradley J. Roth,et al.  The movement of a nerve in a magnetic field: application to MRI Lorentz effect imaging , 2014, Medical & Biological Engineering & Computing.

[46]  Y. Mou,et al.  Effect of low frequency magnetic fields on melanoma: tumor inhibition and immune modulation , 2013, BMC Cancer.

[47]  Y. Mou,et al.  Low Frequency Magnetic Fields Enhance Antitumor Immune Response against Mouse H22 Hepatocellular Carcinoma , 2013, PloS one.

[48]  Hua Wang,et al.  Transforming Growth Factor β1 Signal is Crucial for Dedifferentiation of Cancer Cells to Cancer Stem Cells in Osteosarcoma , 2013, Stem cells.

[49]  S. Kuribayashi,et al.  Computed tomographic appearance of lung tumors treated with percutaneous cryoablation. , 2012, Journal of vascular and interventional radiology : JVIR.

[50]  Jianlin Zhou,et al.  Pulsed electromagnetic fields stimulation prevents steroid-induced osteonecrosis in rats , 2011, BMC musculoskeletal disorders.

[51]  J. Dobson,et al.  Selective activation of mechanosensitive ion channels using magnetic particles , 2007, Journal of The Royal Society Interface.

[52]  Marija Cotic,et al.  Transmembrane potential induced in a spherical cell model under low-frequency magnetic stimulation , 2007, Journal of neural engineering.

[53]  David P. Corey,et al.  TRP channels in mechanosensation: direct or indirect activation? , 2007, Nature Reviews Neuroscience.

[54]  L. Ghibelli,et al.  NMR exposure sensitizes tumor cells to apoptosis , 2006, Apoptosis.

[55]  J. Bergman,et al.  Effects of a magnetic field on pelvic floor muscle function in women with stress urinary incontinence. , 2004, Alternative therapies in health and medicine.

[56]  G. Frankel,et al.  Coiled‐coil proteins associated with type III secretion systems: a versatile domain revisited , 2002, Molecular microbiology.

[57]  G. Dawe,et al.  Changes in neurite outgrowth but not in cell division induced by low EMF exposure: influence of field strength and culture conditions on responses in rat PC12 pheochromocytoma cells. , 2000, Bioelectrochemistry.

[58]  Christian A. Rees,et al.  Molecular portraits of human breast tumours , 2000, Nature.

[59]  J. Schenck The role of magnetic susceptibility in magnetic resonance imaging: MRI magnetic compatibility of the first and second kinds. , 1996, Medical physics.

[60]  L. Pauling Diamagnetic anisotropy of the peptide group. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[61]  D. Worcester,et al.  Structural origins of diamagnetic anisotropy in proteins. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[62]  K. Yarema,et al.  Impact of Static Magnetic Fields (SMFs) on Cells , 2017 .

[63]  Zheng Chun-xi Clinical observation for low-frequency rotating magnetic field treatment of advanced malignant cancer , 2014 .

[64]  Hui Ye,et al.  Transmembrane potential generated by a magnetically induced transverse electric field in a cylindrical axonal model , 2010, Medical & Biological Engineering & Computing.

[65]  Wei Zhang,et al.  Effects of exposure to static magnetic fields (0.2-0.4 T) on the growth and adhesion of tumor cells , 2010 .

[66]  Dmitriy A Yablonskiy,et al.  Protein-induced water 1H MR frequency shifts: contributions from magnetic susceptibility and exchange effects. , 2010, Journal of magnetic resonance.