Universität zu Köln

Orlova, Anna ORCID: 0000-0001-9262-7529, Wagner, Christina, de Araujo, Elvin D., Bajusz, David ORCID: 0000-0003-4277-9481, Neubauer, Heidi A., Herling, Marco, Gunning, Patrick T., Keseru, Gyorgy M. and Moriggl, Richard (2019). Direct Targeting Options for STAT3 and STAT5 in Cancer. Cancers, 11 (12). BASEL: MDPI. ISSN 2072-6694

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Abstract

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 gamma delta 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 targets for small-molecule drug development, but currently there are no direct STAT3/5 inhibitors of clinical grade available. We summarize the development of inhibitors against the SH2 domains of STAT3/5 and discuss their applicability as cancer therapeutics.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Orlova, Anna UNSPECIFIED orcid.org/0000-0001-9262-7529 UNSPECIFIED Wagner, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED de Araujo, Elvin D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bajusz, David UNSPECIFIED orcid.org/0000-0003-4277-9481 UNSPECIFIED Neubauer, Heidi A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Herling, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Gunning, Patrick T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Keseru, Gyorgy M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Moriggl, Richard UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-125408
DOI:	10.3390/cancers11121930
Journal or Publication Title:	Cancers
Volume:	11
Number:	12
Date:	2019
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2072-6694
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SMALL-MOLECULE INHIBITOR; GROWTH-SUPPRESSIVE ACTIVITY; SIGNAL TRANSDUCER; UNPHOSPHORYLATED STAT3; PROSTATE-CANCER; N-DOMAIN; IN-VITRO; TRANSCRIPTION; ACTIVATION; PHOSPHORYLATION Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12540