Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer associated with poor prognosis. As an oncogene, DEK involves in regulation of various cellular metabolisms and plays an important role in tumor growth and progression. Increasing evidences suggested that abnormal expression of DEK is closely related to multiple malignant tumors. However, the possible involvement of DEK in epithelial to mesenchymal transition (EMT) and angiogenesis in TNBC remains unclear. In the present study, we revealed that the over-expression of DEK was significantly correlated with clinical stage, differentiation, and lymph node (LN) metastasis of TNBC and indicated poor overall survival of TNBC patients. Moreover, we demonstrated that DEK depletion could significantly reduce cell proliferation, migration, invasion and angiogenesis in vitro. We also found that DEK promoted cancer cell angiogenesis and metastasis by activating the PI3K/AKT/mTOR pathway. Furthermore, we revealed the inhibitory effect of DEK depletion on tumor growth and progression in a xenograft tumor model in mice. These data indicated that DEK promotes TNBC cell proliferation, angiogenesis, and metastasis via PI3K/AKT/mTOR signaling pathway, and therefore, it might be a potential target in TNBC therapy.
Janus nanoparticles with an anisotropic feature concentrated
multiple
properties on a single carrier, providing synergistic effects. In
this study, dual-functionalized Janus nanoparticles (HA-JMSN/DOX-DMMA)
were constructed with a tumor-targeting ligand (hyaluronic acid, HA)
modified on the one side and a charge reversal group (2,3-dimethylmaleic
anhydride, DMMA) on the other side. The drug release of HA-JMSN/DOX-DMMA
was positively correlated with the acidity of the environment. The
cytotoxicity and cell uptake of HA-JMSN/DOX-DMMA were superior to
the isotropous nanoparticles. The endocytosis pathway of HA-JMSN/DOX-DMMA
involved the clathrin-mediated endocytosis (HA) and the micropinocytosis
(DMMA) at the same time, which indicated that they both participated
in the interaction between nanoparticles and tumor cells. After being
injected intravenously in mice, the distribution of HA-JMSN/DOX-DMMA
in tumor was enhanced significantly. The antitumor therapy study in
vivo showed that HA-JMSN/DOX-DMMA inhibited tumor growth and improved
the survival rate of tumor-bearing mice effectively. In general, HA-JMSN/DOX-DMMA
could take the synergistic effect of active targeting and charge reversal
to deliver drug in tumor cells and kill them efficiently, which was
a promising antitumor nanodrug.
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