Androgen-deprivation remains an important therapeutic option for prostate cancer, and thus castration-resistance is lethal. Despite intense efforts to understand the mechanisms of therapy resistance, the underlying cells remain ill described. We now describe in wild-type (WT) mouse prostates a rare population of luminal progenitor cells that tolerate androgen deprivation and persist or are enriched 2-3 weeks after castration.
Stromal-derived IGF2 promotes colon cancer progression via paracrine and autocrine mechanisms.
The insulin-like growth factor (IGF) signaling axis has an important role in intestinal carcinogenesis and overexpression of IGF2 is an accepted risk factor for colorectal cancer (CRC) development. Genetic amplifications and loss of imprinting contribute to the upregulation of IGF2, but insufficiently explain the extent of IGF2 expression in a subset of patients.
The canonical WNT signaling pathway is crucial for intestinal stem cell renewal and aberrant WNT signaling is an early event in colorectal cancer (CRC) development. A new report in the Journal Oncogene now shows for the first time that WNT2 is one of the most significantly induced genes in CRC stroma as compared to normal stroma. We identified cancer-associated fibroblasts (CAFs) as the main source of WNT2, which activated canonical signaling in colon cancer cells in a paracrine fashion.
The RNA-binding protein tristetraprolin schedules apoptosis of immune cells during bacterial infection.
ZNF683/HOBIT mRNA is preferentially expressed in NK cells compared to other human immune cells. During differentiation, ZNF683/HOBIT mRNA increases and accumulates in parallel to the generation of CD56+ NK cells. Interference with ZNF683/HOBIT expression resulted in a substantial reduction of CD56+ NK cells. However, the proportion of IFN-γ-producing cells appeared to be increased upon ZNF683/HOBIT knockdown.
Ovarian cancer represents the most common gynaecological malignancy and has the highest mortality of all female reproductive cancers. It has a rare predilection to develop brain metastases. Lukas Kenner has now contributed to a report on Next-Generation Sequencing (NGS)-based genomic profiling of brain metastases of primary ovarian cancer. The team from Vienna identified a high number of BRCA-mutations with a NGS study of samples from ovarian carcinoma, besides TP53, ATM and CHEK2 mutations.
The Ludwig Boltzmann Institute for Cancer Research (LBI-CR) consolidates scientific success with outstanding achievements. 2016 was again with respect to publications and the acquisition of external research funds at an unusually high level. Furthermore, the staff of the LBI-CR, together with partner institutions, were able to put significant emphasis on applied and clinically translational cancer research, which was also very popular in the media.
Type I interferons (IFNs) are known to mediate antitumor effects against several tumor types and have therefore been commonly used in clinical anticancer treatment. However, how IFN signaling exerts its beneficial effects is only partially understood. The clinically relevant activity of type I IFNs has been mainly attributed to their role in tumor immune surveillance. Different mechanisms have been postulated to explain how type I IFNs stimulate the immune system. On the one hand, they modulate innate immune cell subsets such as natural killer (NK) cells.
EGFR in tumor-associated myeloid cells promotes development of colorectal cancer in mice and associates with outcomes of patients. Inhibitors of the epidermal growth factor receptor (EGFR) are the first-line therapy for patients with metastatic colorectal tumors without RAS mutations. However, EGFR inhibitors are ineffective in these patients, and tumor level of EGFR does not associate with response to therapy.