Redox signalling regulates breast cancer metastasis via phenotypic and metabolic reprogramming due to p63 activation by HIF1α.

Background: Redox signaling caused by knockdown (KD) of Glutathione Peroxidase 2 (GPx2) in the PyMT mammary tumour model promotes metastasis via phenotypic and metabolic reprogramming. However, the tumour cell subpopulations and transcriptional regulators governing these processes remained unknown.

Methods: We used single-cell transcriptomics to decipher the tumour cell subpopulations stimulated by GPx2 KD in the PyMT mammary tumour and paired pulmonary metastases.

Redox signaling by glutathione peroxidase 2 links vascular modulation to metabolic plasticity of breast cancer.

In search of redox mechanisms in breast cancer, we uncovered a striking role for glutathione peroxidase 2 (GPx2) in oncogenic signaling and patient survival. GPx2 loss stimulates malignant progression due to reactive oxygen species/hypoxia inducible factor-α (HIF1α)/VEGFA (vascular endothelial growth factor A) signaling, causing poor perfusion and hypoxia, which were reversed by GPx2 reexpression or HIF1α inhibition. Ingenuity Pathway Analysis revealed a link between GPx2 loss, tumor angiogenesis, metabolic modulation, and HIF1α signaling.

p21CIP1 Promotes Mammary Cancer-Initiating Cells via Activation of Wnt/TCF1/CyclinD1 Signaling.

Cancer stem cells (CSC) generate and sustain tumors due to tumor-initiating potential, resulting in recurrence or metastasis. We showed that knockout of the cell-cycle inhibitor, p21CIP1, in the PyMT mammary tumor model inhibits metastasis; however the mechanism remained unknown. Here, we show a pivotal role for p21 in potentiating a cancer stem-like phenotype.

Epidermal growth factor receptor-tyrosine kinase inhibitor therapy is especially beneficial to patients with exon 19 deletion compared with exon 21 L858R mutation in non-small-cell lung cancer: Systematic review and meta analysis.

Background: The correlation between epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and EGFR sensitive mutation subtypes in advanced or metastatic non-small cell lung cancer (NSCLC) remains uncertain. We performed this meta-analysis to determine different clinical outcomes between patients with exon 19 deletion accepting EGFR-TKI therapy compared with those with exon 21 L858R mutation.

Methods: PubMed and Web of Science were analyzed for eligible trials.

Randomized controlled trials of induction treatment and surgery versus combined chemotherapy and radiotherapy in stages IIIA-N2 NSCLC: a systematic review and meta-analysis.

Background: The efficacy of induction treatment plus surgery for improving postoperative survival in patients with non-small-cell lung cancer (NSCLC) in stages IIIA-N2 is controversial, especially compared with the combined chemotherapy and radiotherapy. We therefore performed a systematic review and meta-analysis of the published phase III randomized clinical trials (RCTs) to quantitatively evaluate the survival benefit of preoperative induction treatment vs. combined chemoradiotherapy.