Identification of genomic binding sites and direct target genes for the transcription factor DDIT3/CHOP.

DDIT3 is a tightly regulated basic leucine zipper (bZIP) transcription factor and key regulator in cellular stress responses. It is involved in a variety of pathological conditions and may cause cell cycle block and apoptosis. It is also implicated in differentiation of some specialized cell types and as an oncogene in several types of cancer.

Different HSP90 Inhibitors Exert Divergent Effect on Myxoid Liposarcoma In Vitro and In Vivo.

The therapeutic options for patients with relapsed or metastatic myxoid liposarcoma (MLS) remain scarce and there is currently no targeted therapy available. Inhibition of the HSP90 family of chaperones has been suggested as a possible therapeutic option for patients with MLS. However, the clinical effect of different HSP90 inhibitors vary considerably and no comparative study in MLS has been performed.

FUS-DDIT3 Fusion Oncoprotein Expression Affects JAK-STAT Signaling in Myxoid Liposarcoma.

Myxoid liposarcoma is one of the most common sarcoma entities characterized by FET fusion oncogenes. Despite a generally favorable prognosis of myxoid liposarcoma, chemotherapy resistance remains a clinical problem. This cancer stem cell property is associated with JAK-STAT signaling, but the link to the myxoid-liposarcoma-specific FET fusion oncogene is not known.

FET fusion oncoproteins interact with BRD4 and SWI/SNF chromatin remodelling complex subtypes in sarcoma.

FET fusion oncoproteins containing one of the FET (FUS, EWSR1, TAF15) family proteins juxtaposed to alternative transcription-factor partners are characteristic of more than 20 types of sarcoma and leukaemia. FET oncoproteins bind to the SWI/SNF chromatin remodelling complex, which exists in three subtypes: cBAF, PBAF and GBAF/ncBAF. We used comprehensive biochemical analysis to characterize the interactions between FET oncoproteins, SWI/SNF complexes and the transcriptional coactivator BRD4.

FET family fusion oncoproteins target the SWI/SNF chromatin remodeling complex.

Members of the human FET family of RNA-binding proteins, comprising FUS, EWSR1, and TAF15, are ubiquitously expressed and engage at several levels of gene regulation. Many sarcomas and leukemias are characterized by the expression of fusion oncogenes with FET genes as 5' partners and alternative transcription factor-coding genes as 3' partners. Here, we report that the N terminus of normal FET proteins and their oncogenic fusion counterparts interact with the SWI/SNF chromatin remodeling complex.

JAK-STAT signalling controls cancer stem cell properties including chemotherapy resistance in myxoid liposarcoma.

Myxoid liposarcoma (MLS) shows extensive intratumoural heterogeneity with distinct subpopulations of tumour cells. Despite improved survival of MLS patients, existing therapies have shortcomings as they fail to target all tumour cells. The nature of chemotherapy-resistant cells in MLS remains unknown.