There is great interest in understanding how the cancer stem cell population may be maintained in solid tumors. Here we show that tumor cells exhibiting stem-like properties and expression of pluripotency markers NANOG and OCT4 can arise from original differentiated tumor cells freshly isolated from human glioblastomas and which have never known any serum culture conditions. Induction of EGR1 by EGFR/ERK signaling promoted cell conversion from a less aggressive, more differentiated cellular state...
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Cellular senescence is a potent tumor-suppressive program that prevents neoplastic events. Paradoxically, senescent cells develop an inflammatory secretome, termed the senescence-associated secretory phenotype (SASP), which is implicated in age-related pathologies including cancer. Here we report that senescent cells actively synthesize and release small extracellular vesicles (sEVs) with a distinctive size distribution. Mechanistically, SIRT1 loss supported accelerated sEV production despite enhanced...
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As sequencing becomes more economical, we are identifying sequence variations in the population faster than ever. For disease-associated genes, it is imperative that we differentiate a sequence variant as either benign or pathogenic such that the appropriate therapeutic interventions or surveillance can be implemented. PTEN (Phosphatase and TENsin homolog) is a frequently mutated tumor suppressor that has been linked to the PTEN hamartoma tumor syndrome. While the domain structure of PTEN and the...
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HACE1 is an E3 ubiquitin ligase with important roles in tumor biology and tissue homeostasis. Loss or mutation of HACE1 has been associated with the occurrence of a variety of neoplasms, but the underlying mechanisms have not been defined yet. Here we report that HACE1 is frequently mutated in human lung cancer. In mice, loss of Hace1 led to enhanced progression of KRasG12D-driven lung tumors. Additional ablation of the oncogenic GTPase Rac1 partially reduced progression of Hace1-/- lung tumors....
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Bone is the most common metastatic site for breast cancer. Although the estrogen-related receptor alpha (ERRα) has been implicated in breast cancer cell dissemination to the bone from the primary tumor, its role after tumor cell anchorage in the bone microenvironment remains elusive. Here, we reveal that ERRα inhibits the progression of bone metastases of breast cancer cells by increasing the immune activity of the bone microenvironment. Overexpression of ERRα in breast cancer bone metastases induced...
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Interleukin-26 (IL-26) is a unique amphipathic member of the IL-10 family of cytokines that participates in inflammatory signaling through a canonical receptor pathway. It also directly binds DNA to facilitate cellular transduction and intracellular inflammatory signaling. While IL-26 has almost no described role in cancer, our in vivo screen of inflammatory and cytokine pathway genes revealed IL-26 to be one of the most significant inflammatory mediators of mammary engraftment and lung metastatic...
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British Journal of Cancer, Published online: 05 May 2020; doi:10.1038/s41416-020-0852-4Isocitrate dehydrogenase 2 contributes to radiation resistance of oesophageal squamous cell carcinoma via regulating mitochondrial function and ROS/pAKT signalling
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British Journal of Cancer, Published online: 05 May 2020; doi:10.1038/s41416-020-0857-zSurvival benefit of tamoxifen in male breast cancer: prospective cohort analysis
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British Journal of Cancer, Published online: 05 May 2020; doi:10.1038/s41416-020-0860-4Use of proton pump inhibitors and histamine-2 receptor antagonists and risk of gastric cancer in two population-based studies
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The cholesterol biosynthesis pathway is typically upregulated in breast cancer. The role of NAD(P)-dependent steroid dehydrogenase-like (NSDHL) gene, which is involved in cholesterol biosynthesis, in breast ca...
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The adhesion molecule, FAT4, has a tumor suppressor function with a critical role in the epithelial-to-mesenchymal-transition (EMT) and anti-malignant growth in several cancers. No study has investigated yet i...
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Lomustine, also known as CCNU (chloroethyl-cyclohexyl-nitrosourea), is an alkylating agent of the nitrosourea family [1,2,3] (Fig. 1). It is a monofunctional alkylating agent which alkylates DNA and RNA and can cross-link DNA and thus acts in a cell cycle-dependent and -independent manner. One of the most relevant lesions induced by lomustine, the formation of O6-chloroethylguanine, can be reverted by O6-methylguanine DNA methyltransferase (MGMT). Lomustine may also inhibit enzymatic functions by...
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Pancreatic adenocarcinoma (PA) is expected to be the 4th leading cause of cancer-related death, with 47 050 deaths projected to occur in 2020 in the United States [1]. Its 5-year survival rate is one of the worst in the field of oncology and is <10% for all stages taken together [2]. GLOBOCAN predicts a trend towards increased PA incidence (+77.7%, with 356 358 new cases) and mortality (+79.9%, with 345 181 deaths) from 2018 to 2040 [3]. PA may even become the 3rd leading cause of death from cancer...
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Immune checkpoint inhibitors (ICI) have improved the outcomes for patients with advanced cancers, also resulting in increased numbers of long-term survivors in subgroups of patients with metastatic disease or irresectable tumors. In advanced stage melanoma, for example, a pooled analysis has shown an overall survival (OS) rate of 20% at 10 years in patients treated with ipilimumab. An OS rate of 34% at 5 years was seen when given a programmed cell death protein 1 (PD-1) antibody, for treatment-naïve...
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