Metastatic melanoma is characterised by metabolic abnormalities. But how aggressive tumor behaviour is altered by metabolic state remains ill understood. Researchers from Vienna in collaboration with the LBI-CR now report high-density lipoprotein (HDL) receptor SR-BI expression can predict melanoma progression in patients. The metastasis-associated epithelial-to-mesenchymal transition (EMT) was perturbed by SR-BI knockdown, but not functional inhibition of its cholesterol transporting capacity.
T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive T-lymphoid malignancy usually refractory to current treatment strategies and associated with a short overall survival. A group of researchers from Vienna led by CeMM and in collaboration with colleagues from the LBI-CR pursued to identify novel effective treatments for T-PLL patients by functional testing of primary patient-derived lymphoma cells using a library of 106 FDA-approved anti-cancer drugs or compounds currently in clinical development.
Group Picture of the first AustroMetabolism Workshop held at CeMM on 28 September 2017
The p53 tumor suppressor is inactivated in most cancers, thus suggesting that loss of p53 is a prerequisite for tumor growth. Therefore, its reintroduction through different means bears great clinical potential. Kenner and colleagues review small molecules, which are currently developed and able to reactivate specific, frequently observed mutant forms of p53 or that inhibit the negative regulator MDM2.
Stem cells have the property to induce the invasion of primary somatic cells through insulin-like growth factor I (IGF-I)- or II (IGF-II)-mediated activation of mechanistic target of rapamycin complex 1 (mTORC1). We propose downstream of mTORC1 stem cell-induced invasion is mediated by hypoxia-inducible factor 1-alpha (HIF-1α)-regulated matrix metalloproteinases. Human stem cells use this mechanism to induce invasion and thereby attract cells from the microenvironment in vivo.
Lukas Kenner and colleagues report patients suffering from oropharyngeal squamous cell carcinoma without detectable p16 may benefit from postoperative radiotherapy, whereas p16-positive patients do not benefit from additional treatment. The report is now online in the journal Laryngoscope.
Signal transducers and activators of transcription (STATs) are latent, cytoplasmic transcription factors. Janus kinases (JAKs) and activated CDC42-associated kinase-1 (ACK1/TNK2) catalyse the phosphorylation of STAT1 and the expression of its target genes. Here we demonstrate that catalytically active ACK1 promotes the phosphorylation and nuclear accumulation of STAT1 in transformed kidney cells.
Chronic myeloid leukemia (CML) is increasingly treated with the BCR/ABL1 inhibitor Nilotinib. Although otherwise well-tolerated, Nilotinib has been associated with progressive arterial occlusive disease (AOD). Our objective was to determine the exact frequency of AOD and examine effects of Nilotinib and Imatinib on endothelial cells to explain AOD-development. In contrast to Imatinib, Nilotinib was found to upregulate pro-atherogenic adhesion-proteins (ICAM-1, E-selectin, VCAM-1) on human endothelial cells.
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.