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Breast cancer is the second most cancer worldwide in females. The primary factor responsible for tumor recurrence is the presence of breast cancer stem cells (BCSCs), which escape the chemo-radiotherapy. In this study, we have investigated the role of Secretory phospholipase-A2 Group 2A (sPLA 2 -IIA) that is overexpressed in BCSCs of MCF7 and MDA-MB-231 breast cancer cell lines. Further, overexpression of sPLA 2 -IIA revealed an increased EGFR/JNK/c-JUN/c-FOS signaling in BCSCs, while sPLA 2 -IIA knockdown significantly reduced the percentage of BCSCs and decreased signaling in both the cell lines. Importantly, sPLA 2 -IIA knockdown showed differentiation of BCSCs. Strikingly, PET imaging showed a decreased metastatic potential of BCSCs. Our study revealed a novel role of sPLA 2 -IIA in regulating BCSCs, which play a crucial role in regulating the differentiation and metastatic potential of BCSCs. [Display omitted] • SPLA2-IIA knockdown reduces the number of BCSCs. • Loss of sPLA2-IIA decreases the tumorigenic potential of BCSCs in NOD/SCID mice. • SPLA2-IIA knockdown enhances the differentiation potential of BCSCs. • SPLA2-IIA knockdown leads to a decrease in the metastatic potential of BCSCs. • SPLA2-IIA knockdown reduces the EGFR/JNK/c-JUN-c-FOS signaling in BCSCs. [ABSTRACT FROM AUTHOR]

Breast cancer stem cells (BCSCs) are slow cycling cells that escape the traditional chemo-radio-therapy, thereby contributing in resistance and recurrence. Although several markers have been identified, it is still challenging to develop strategies targeting them. In this study, we have isolated BCSCs from MCF-7 cell line using markers CD44+/CD24-/low, which showed higher percentage of mammospheres in CSC population. Moreover, in vivo tumorigenic potential of BCSCs showed as low as 10,000 cells had the ability to develop tumors when transplanted into NOD-SCID mice. We observed an increased level of EMT markers in CSC population. Overexpression of secretory phospholipase sPLA 2 -IIA was found in CSCs. Further, we have uncovered the upregulation of sPLA 2 -IIA mediated through JNK signaling in breast cancer cells whereas knockdown of sPLA 2 -IIA reduces JNK signaling, cell proliferation, EMT and in vivo tumorigenic potential in breast cancer cells. Our study reveals overexpression of sPLA 2 -IIA in two different breast cancer cells such as MCF7 (ER+,PR+) and a triple negative, MDA-MB-231 (ER-PR-HER2-). Further, the novel role of sPLA 2 -IIA was discerned by unraveling the molecular mechanism, which regulates the cell proliferation and metastasis in breast cancer cells. [Display omitted] • SPLA 2 -IIA mediated JNK signaling increases proliferation, tumorigenecity and metastatic potential in breast cancer. • SPLA 2 -IIA knockdown reduces the tumorigenic and metastatic potential in two different cell lines MCF7 and MDA-MB-231. • MCF7 cancer stem cells showed an increased tumorigenic potential and EMT markers. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is a highly aggressive carcinoma with a high incidence of recurrence and distant metastasis. However, the mechanism of epithelial to mesenchymal transition (EMT) during tumor progression and metastasis in OSCC has not yet been fully elucidated. It is well known that the Cl− channel controls cell volume and activates several signaling pathways for cell differentiation. The aim of the present study was to investigate the role of the Cl− channel on EMT in the OSC 20 cell line, which is an OSCC line. OSC-20 cells were cultured with low serum medium containing a Cl− channel blocker NPPB. Morphological changes, gene expression, immunoreactivity, cell volume, and signaling pathway of the NPPB-treated OSC-20 cells were evaluated. The NPPB-treated OSC-20 cells showed typical morphology of mesenchymal cells. The expression levels of the epithelial marker E-cadherin in the NPPB-treated OSC-20 cells were lower than those of the untreated and TGF-β1-treated OSC-20 cells. On the other hand, mesenchymal markers such as vimentin, ZEB1, and Snail, in the NPPB-treated OSC-20 cells were higher than those in the untreated and TGF-β1-treated OSC-20 cells. Furthermore, a large number of vimentin-positive cells also appeared in the NPPB-treated OSC-20 cells. Additionally, the cell volume of these cells was significantly increased compared to that of the untreated and TGF-β1-treated cells. Interestingly, NPPB did not activate the TGF-β/smad signaling pathway, but activated the Wnt/β-catenin signaling pathway. These results suggest that Cl− channel dysfunction promoted EMT via activation of the Wnt/β-catenin signaling pathway in OSCC. • The NPPB-treated OSC-20 cells showed typical morphology of mesenchymal cells. • The NPPB-treated OSC-20 cells expressed mesenchymal markers. • NPPB activated the Wnt/β-catenin signaling pathway in the OSC-20 cells. • Dysfunction of Cl− channels promoted EMT. [ABSTRACT FROM AUTHOR]

Proliferative vitreoretinopathy (PVR) is a common complication of open globe injury and the most common cause of failed retinal detachment surgery. The response by retinal pigment epithelial (RPE) cells liberated into the vitreous includes proliferation and migration; most importantly, epithelial to mesenchymal transition (EMT) of RPE plays a central role in the development and progress of PVR. For the first time, we show that knockdown of BIRC5, a member of the inhibitor of apoptosis protein family, using either lentiviral vector based CRISPR/Cas9 nickase gene editing or inhibition of survivin using the small-molecule inhibitor YM155, results in the suppression of EMT in RPE cells. Knockdown of survivin or inhibition of survivin significantly reduced TGFβ-induced cell proliferation and migration. We further demonstrated that knockdown or inhibition of survivin attenuated the TGFβ signaling by showing reduced phospho-SMAD2 in BIRC5 knockdown or YM155-treated cells compared to controls. Inhibition of the TGFβ pathway using TGFβ receptor inhibitor also suppressed survivin expression in RPE cells. Our studies demonstrate that survivin contributes to EMT by cross-talking with the TGFβ pathway in RPE cells. Targeting survivin using small-molecule inhibitors may provide a novel approach to treat PVR disease. [ABSTRACT FROM AUTHOR]

Highlights: [•] This study generates a monoclonal antibody CA27 against the mycoplasmal p37 protein. [•] CA27 isolates circulating tumor cells (CTCs) from the blood of liver cancer patients. [•] Results show the first evidence for mycoplasma infected-CTCs in cancer patients. [ABSTRACT FROM AUTHOR]

Highlights: [•] FAK induces a mesenchymal/epithelial switch affecting cell–cell cohesion. [•] FAK influences the macroscopic cell colony spreading in two and three dimensions. [•] FAK affects cellular velocity fields, persistence, and correlation length. [ABSTRACT FROM AUTHOR]