Cancers, Vol. 11, Pages 1930: Direct Targeting Options for STAT3 and STAT5 in Cancer

Cancers, Vol. 11, Pages 1930: Direct Targeting Options for STAT3 and STAT5 in Cancer Cancers doi: 10.3390/cancers11121930 Authors: Anna Orlova Christina Wagner Elvin D. de Araujo Dávid Bajusz Heidi A. Neubauer Marco Herling Patrick T. Gunning György M. Keserű Richard Moriggl Signal transducer and activator of transcription (STAT)3 and STAT5 are important transcription factors that are able to mediate or even drive cancer progression through hyperactivation or gain-of-function mutations. Mutated STAT3 is mainly associated with large granular lymphocytic T-cell leukemia, whereas mutated STAT5B is associated with T-cell prolymphocytic leukemia, T-cell acute lymphoblastic leukemia and γδ T-cell-derived lymphomas. Hyperactive STAT3 and STAT5 are also implicated in various hematopoietic and solid malignancies, such as chronic and acute myeloid leukemia, melanoma or prostate cancer. Classical understanding of STAT functions is linked to their phosphorylated parallel dimer conformation, in which they induce gene transcription. However, the functions of STAT proteins are not limited to their phosphorylated dimerization form. In this review, we discuss the functions and the roles of unphosphorylated STAT3/5 in the context of chromatin remodeling, as well as the impact of STAT5 oligomerization on differential gene expression in hematopoietic neoplasms. The central involvement of STAT3/5 in cancer has made these molecules attractive ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research