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

Loukik Arora; Alan Prem Kumar; Frank Arfuso; Wee Joo Chng; Gautam Sethi

doi:10.3390/cancers10090327

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

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

Authors

Loukik Arora¹, Alan Prem Kumar^{2

3

4

5

6}, Frank Arfuso⁷, Wee Joo Chng^{8

9}, Gautam Sethi^{10

11}

Affiliations

¹ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore. arora.loukik@u.nus.edu.
² Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore. csiapk@nus.edu.sg.
³ Cancer Science Institute of Singapore, Centre for Translational Medicine, 14 Medical Drive, #11-01M, Singapore 117599, Singapore. csiapk@nus.edu.sg.
⁴ Medical Science Cluster, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore. csiapk@nus.edu.sg.
⁵ Curtin Medical School, Faculty of Health Sciences, Curtin University, Perth, WA 6102, Australia. csiapk@nus.edu.sg.
⁶ National University Cancer Institute, National University Health System, Singapore 119074, Singapore. csiapk@nus.edu.sg.
⁷ Stem Cell and Cancer Biology Laboratory, School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6102, Australia. frank.arfuso@curtin.edu.au.
⁸ Cancer Science Institute of Singapore, Centre for Translational Medicine, 14 Medical Drive, #11-01M, Singapore 117599, Singapore. mdccwj@nus.edu.sg.
⁹ Department of Hematology-Oncology, National University Cancer Institute, National University Health System, Singapore 119074, Singapore. mdccwj@nus.edu.sg.
¹⁰ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore. phcgs@nus.edu.sg.
¹¹ School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6009, Australia. phcgs@nus.edu.sg.

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.

Publication types

Review