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PAK2 promising target for leukemia

The p21-activated kinases (PAKs) are key nodes in oncogenic signalling pathways controlling growth, survival, and motility of cancer cells. Their activity is increased in many human cancers and is associated with poor prognosis. We show now that PAK1 and PAK2 are the critical isoforms in a BCR/ABL1+ haematopoietic malignancy. In suspension, leukaemic cells deficient for PAK1 and PAK2 undergo apoptosis, while the loss of either protein is well tolerated. However, we found that leukaemic cells explicitly require PAK2 to grow towards an extracellular matrix.

Targeting STATs to overcome drug resistance in chronic myeloid leukemia

In chronic myeloid leukemia BCR-ABL1 mutations and activation of additional pro-oncogenic pathways  cause therapy resistance. Drug combinations covering a broad range of targets may overcome resistance.We investigated a compound that inhibits proliferation and survival of tyrosine kinase inhibitor-resistant BCR-ABL1+ cell lines. Succesful drug-combinations blocked multiple signalling cascades and molecules, including STAT3 and STAT5.

Castration-resistant progenitor cell population might be origin of relapse

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.

New paper on IGF2 promoting colon cancer progression

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. 

New paper on WNT signaling in colorectal carcinoma

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.

New paper on transcription factor ZNF683/HOBIT regulating immune-cells

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.

New paper out on BRCA-mutations in brain metastasis

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.