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Review
. 2018 Sep 13;10(9):327.
doi: 10.3390/cancers10090327.

The Role of Signal Transducer and Activator of Transcription 3 (STAT3) and Its Targeted Inhibition in Hematological Malignancies

Loukik Arora  1 , Alan Prem Kumar  2   3   4   5   6 , Frank Arfuso  7 , Wee Joo Chng  8   9 , Gautam Sethi  10   11
Affiliations
Review

The Role of Signal Transducer and Activator of Transcription 3 (STAT3) and Its Targeted Inhibition in Hematological Malignancies

Loukik Arora et al. Cancers (Basel). .

Abstract

Signal transducer and activator of transcription 3 (STAT3), a member of the STAT protein family, can be phosphorylated by receptor-associated Janus kinases (JAKs) in response to stimulation by cytokines and growth factors. It forms homo- or heterodimers that can translocate to the cell nucleus where they act as transcription activators. Constitutive activation of STAT3 has been found to be associated with initiation and progression of various cancers. It can exert proliferative as well as anti-apoptotic effects. This review focuses on the role of STAT3 in pathogenesis i.e., proliferation, differentiation, migration, and apoptosis of hematological malignancies viz. leukemia, lymphoma and myeloma, and briefly highlights the potential therapeutic approaches developed against STAT3 activation pathway.

Keywords: STAT3; anti-apoptosis; hematological malignancies; proliferation; targeted inhibition.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The molecular structure of the two STAT3 isoforms. The STAT3 molecule consists of several distinct domains:(i) the N-terminal domain containing an oligomerization and a coiled-coil domain, (ii) the DNA-binding domain, (iii) the linker domain, (iv) the Src homology 2 (SH2) domain, and (v) the C-terminal Transactivation domain (TAD). STAT3α is the full-length STAT3 protein, with a TAD at the C terminal that has a serine residue at position 727. STAT3β is the truncated STAT3 protein, without the TAD.
Figure 2
Figure 2
A schematic representation of STAT3 signaling cascade. STAT proteins are present in an inactive (unphosphorylated latent dimers) form in the cytoplasm. Upon ligand binding, the receptors dimerize to recruit upstream JAK/Src kinases. Phosphorylated tyrosine residues on the receptors provide a docking site to STATs and bring about their phosphorylation and activation. Phosphorylated STATs upon translocation to nucleus bind onto the consensus sequence and thereby regulate gene transcription.
Figure 3
Figure 3
Various potential strategies for STAT3 inhibition.
See this image and copyright information in PMC

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