Colorectal cancer (CRC) is a common cancer with high morbidity and mortality.1 Post-translational modification (PTM) of protein plays an important role in the pathogenesis of CRC. Lysine crotonylation (Kcr) is an impo...Colorectal cancer (CRC) is a common cancer with high morbidity and mortality.1 Post-translational modification (PTM) of protein plays an important role in the pathogenesis of CRC. Lysine crotonylation (Kcr) is an important type of PTM and has been proved evolutionarily conserved in eukaryotic cells from a wide range of species.2 However, the role of protein Kcr in the progression of CRC is unclear.展开更多
Breast cancer is a common malignancy in women with disappointing prognosis especially the triple-negative subtype.Recently,nanomedicine becomes a promising therapeutic strategy for breast cancer,such as platinum nanop...Breast cancer is a common malignancy in women with disappointing prognosis especially the triple-negative subtype.Recently,nanomedicine becomes a promising therapeutic strategy for breast cancer,such as platinum nanoparticles(PtNPs).Despite the promising anticancer effects of PtNPs,the safety of PtNPs remains to be fully evaluated.Herein,a series of cell and animal experiments demonstrate that PtNPs facilitate breast cancer metastasis by damaging the vascular endothelial barrier.PtNPs disrupt endothelial cell proliferation,migration and tube-like structure formation,destruct endothelial adhesions junctions and induce endothelial barrier leakiness in vitro most likely by stimulating intracellular reactive oxygen species(ROS)generation and altering the expression and conformation of endothelial junctional proteins,thus promoting intravasation and extravasation of the implanted 4T1 breast cancer cells and leading to cancer metastasis in female BALB/c nude mice in vivo.In addition,smaller PtNPs(5 nm)are more potent than larger PtNPs(70 nm)in exerting the above effects.The study provides the first evidence that PtNPs can promote breast cancer metastasis by damaging endothelial barrier.The unexpected detrimental effects of PtNPs should be considered in future nanomedicine designs for the treatment of breast cancer.展开更多
基金supported by Key Medical Science and Technology Program of Shanxi Province(No.2020XM01)Shanxi“1331 Project”Quality and Efficiency Improvement Plan(No.1331KFC)+1 种基金Shanxi University of Chinese Medicine Science and Technology Innovation Ability Training Project(No.2019PY-016)partially by the National Natural Science Foundation of China(No.82170523).
文摘Colorectal cancer (CRC) is a common cancer with high morbidity and mortality.1 Post-translational modification (PTM) of protein plays an important role in the pathogenesis of CRC. Lysine crotonylation (Kcr) is an important type of PTM and has been proved evolutionarily conserved in eukaryotic cells from a wide range of species.2 However, the role of protein Kcr in the progression of CRC is unclear.
基金the Key Medical Science and Technology Program of Shanxi Province(No.2020XM01)Shanxi“1331”Project Quality and Efficiency Improvement Plan(No.1331KFC)+2 种基金Applied Basic Research Program of Shanxi Province(Nos.201801D221408 and 201901D211320)Supporting Project for Returned Overseas Researchers of Shanxi Province(No.2020-081)partially by the National Natural Science Foundation of China(Nos.81801858,22007063,and 82170523)。
文摘Breast cancer is a common malignancy in women with disappointing prognosis especially the triple-negative subtype.Recently,nanomedicine becomes a promising therapeutic strategy for breast cancer,such as platinum nanoparticles(PtNPs).Despite the promising anticancer effects of PtNPs,the safety of PtNPs remains to be fully evaluated.Herein,a series of cell and animal experiments demonstrate that PtNPs facilitate breast cancer metastasis by damaging the vascular endothelial barrier.PtNPs disrupt endothelial cell proliferation,migration and tube-like structure formation,destruct endothelial adhesions junctions and induce endothelial barrier leakiness in vitro most likely by stimulating intracellular reactive oxygen species(ROS)generation and altering the expression and conformation of endothelial junctional proteins,thus promoting intravasation and extravasation of the implanted 4T1 breast cancer cells and leading to cancer metastasis in female BALB/c nude mice in vivo.In addition,smaller PtNPs(5 nm)are more potent than larger PtNPs(70 nm)in exerting the above effects.The study provides the first evidence that PtNPs can promote breast cancer metastasis by damaging endothelial barrier.The unexpected detrimental effects of PtNPs should be considered in future nanomedicine designs for the treatment of breast cancer.
