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Centrosome-localized mitotic Aurora kinase A (AURKA) facilitates G2/M events. Here we show that AURKA translocates to the nucleus and causes distinct oncogenic properties in malignant cells by enhancing breast cancer stem cell (BCSC) phenotype. Unexpectedly, this function is independent of its kinase activity. Instead, AURKA preferentially interacts with heterogeneous nuclear ribonucleoprotein K (hnRNP K) in the nucleus and acts as a transcription factor in a complex that induces a shift in MYC promoter usage and activates the MYC promoter. Blocking AURKA nuclear localization inhibits this newly discovered transactivating function of AURKA, sensitizing resistant BCSC to kinase inhibition. These findings identify a previously unknown oncogenic property of the spatially deregulated AURKA in tumorigenesis and provide a potential therapeutic opportunity to overcome kinase inhibitor resistance. Aurora kinase A is a mitotic kinase that facilitates G2/M events. Here the authors show that in breast cancer cells Aurora kinase A has a kinase-independent function in the nucleus by activating the MYC promoter in cooperation with hnRNP K, enhancing the breast cancer stem cell phenotype.

Polymyositis (PM) is a very rare paraneoplastic syndrome in association with breast cancer, here we present a breast cancer patient with a sudden onset of respiratory failure caused by PM. A 47-year-old woman, with a history of a lump in her right breast for 3 months, weakness and anorexia for about 1 month, suddenly presented with respiratory failure and elevated muscle enzymes. Muscle biopsy revealed myositis and breast biopsy was consistent with invasive ductal breast cancer. Decreases of muscle enzyme levels were observed after corticosteroid therapy and the lumpectomy, but the patient died from respiratory failure. A case of respiratory failure caused by breast cancer associated polymyositis was presented. This case server to remind that breast cancer patients with muscle weakness or muscle enzyme elevation may be involved with PM.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited effective treatment options. New therapeutic approaches are urgently needed to improve the prognosis of TNBC. Here we demonstrated that a redox modulator, selenocystine (SeC), significantly inhibits TNBC cell proliferation in a dose- and time-dependent manner. Through cell apoptosis assays and cell cycle distribution analyses, we have shown that the in vitro inhibitory effect of SeC on TNBC cells can be attributed to the induction of apoptosis and the S-phase arrest in a dose-dependent manner. Therefore, this finding implies that SeC potentially is a novel therapeutic agent for TNBC.

Previous studies have demonstrated strong anti-tumor effects of ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F), an extract from Pteris semipinnata, in liver, lung, stomach and anaplastic thyroid cancer cells. However, whether 5F inhibits the growth of breast cancer cells remains unclear. The present study assessed the effect of 5F on breast cancer cells. The breast cancer cell lines MCF-7, MDA-MB-231 and SK-BR-3 were each treated with 0, 5, 10, 20 and 40 µg/ml 5F. Morphological changes in the breast cancer cells were assessed using fluorescence microscopy. The proliferation and apoptosis of the breast cancer cells were also examined using Cell Counting Kit-8 and flow cytometry. The levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X apoptosis regulator (Bax), Bcl-2 antagonist/killer (Bak) 1 and caspase-3 in the breast cancer cells were assessed. The results of the present study demonstrated that 5F inhibited the proliferation of MCF-7, MDA-MB-231 and SK-BR-3 breast cancer cells in a concentration- and time-dependent manner. Treatment with 5F also induced the apoptosis of breast cancer cells. MDA-MB-231, MCF-7, and SK-BR-3 cells exhibited apoptotic rates of 40.13, 60.44, and 70.49%, respectively, following incubation with 5F for 24 h. Furthermore, 5F significantly decreased the expression of Bcl-2 and increased the expression of Bax, Bak, and caspase-3 in a concentration-dependent manner. The results of the present study revealed that the P. semipinnata extract 5F inhibited the growth of human breast cancer cells in a time- and concentration-dependent manner, and that 5F induced apoptosis of human breast cancer cells.

Previous studies have demonstrated strong anti-tumor effects of ent-11[alpha]-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F), an extract from Pteris semipinnata, in liver, lung, stomach and anaplastic thyroid cancer cells. However, whether 5F inhibits the growth of breast cancer cells remains unclear. The present study assessed the effect of 5F on breast cancer cells. The breast cancer cell lines MCF-7, MDA-MB-231 and SK-BR-3 were each treated with 0, 5, 10, 20 and 40 [micro]g/ml 5F. Morphological changes in the breast cancer cells were assessed using fluorescence microscopy. The proliferation and apoptosis of the breast cancer cells were also examined using Cell Counting Kit-8 and flow cytometry. The levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X apoptosis regulator (Bax), Bcl-2 antagonist/killer (Bak) 1 and caspase-3 in the breast cancer cells were assessed. The results of the present study demonstrated that 5F inhibited the proliferation of MCF-7, MDA-MB-231 and SK-BR-3 breast cancer cells in a concentration-and time-dependent manner. Treatment with 5F also induced the apoptosis of breast cancer cells. MDA-MB-231, MCF-7, and SK-BR-3 cells exhibited apoptotic rates of 40.13, 60.44, and 70.49%, respectively, following incubation with 5F for 24 h. Furthermore, 5F significantly decreased the expression of Bcl-2 and increased the expression of Bax, Bak, and caspase-3 in a concentration-dependent manner. The results of the present study revealed that the P. semipinnata extract 5F inhibited the growth of human breast cancer cells in a time-and concentration-dependent manner, and that 5F induced apoptosis of human breast cancer cells.

ObjectivesOur study objective was to explore whether abnormalities in the subtypes of T cells and B cells were present in peripheral blood of patients with osteoarthritis (OA) and healthy controls (HCs).MethodDemographic and clinical variables and blood were collected. OA severity was measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire. Flow cytometry was used to establish the frequencies of lineage subsets. Monoclonal antibodies against 21 surface markers were used to distinguish and evaluate T cells’ and B cells’ subpopulation. The proportion of each subset was compared and correlations between age, immune cells, and clinical data were analyzed.ResultsA total of 30 OA patients (male/female = 9/21) and 45 HCs (male/female = 14/31) were included. Median WOMAC pain was 3.0 (2.0). There was no difference in the proportion of T cells, CD8+ T cells, and B cells (p > 0.05). The proportion of CD4+ T cells was higher in OA groups, together with an increased CD4 to CD8 ratio (p = 0.016). CD8+CD45RA+ T cells were reduced after adjustment for age, while CD8+CD45RA− T cells were elevated in OA (p < 0.05). CD4+CD45RA−CCR7+ T cells and CD4+CD45RA−CCR7− T cells were increased (p < 0.004). The proportion of T helper (Th) 17 and T follicular helper (Tfh) 2 cells was higher, but cytotoxic T (Tc) 17 cells were fewer in OA (p < 0.05). CD3−CD19+IgD−IgM−CD27+CD38+ B cells were decreased in OA (p ≤ 0.001). The WOMAC pain score correlated with CD3+CD4+CXCR5−PD-1+ T cells positively (B = 0.404, p = 0.027). CD3−CD19+CD27−IgD+ cells correlated negatively with erythrocyte sedimentation rate (ESR) (B = −0.550, p = 0.005).ConclusionsThe T cell and B cell profiles were proved to have alteration suggesting that acquired immune system may play a substantial role in the pathogenesis of OA.Key Points• The T cell and B cell profiles were proved to have alteration suggesting that acquired immune system may play a substantial role in the pathogenesis of OA.• The WOMAC pain score correlated with CD3+CD4+CXCR5−PD-1+ T cells and T helper 17 cells positively.• Memory T cells were increased in OA patients, suggesting they could play an important role in OA.