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Targeting key transcriptional factor STAT3 in colorectal cancer

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Abstract

In developed countries, colorectal cancer (CRC) is the fourth most common cancer and the second leading cause of malignant-related deaths. CRC is treatable cancer when diagnosed early; however, diagnosis at the advanced stage is associated with a poor prognosis. Although chemotherapy is generally very promising, STAT3 protein which is overexpressed and persistently activated in CRC cells is observed to be the major contributor of chemoresistance development. It has been shown to play a prominent and pathogenic role in CRC initiation, progression, and metastasis. While over the past few years, research has been focused on STAT3 which is expressed at the center of various oncogenic pathways. This review is a discussion of the oncogenic role of STAT3 in CRC and potential therapeutic STAT3 inhibitors and analogs used to control and treat CRC.

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Abbreviations

5-FU:

5-Fluoro uracil

ASO:

Antisense oligonucleotide

Bax:

Bcl-2 associated x protein

Bcl-2:

B-cell lymphoma 2

CCND2:

Cell cycle cyclin D2

CMTM4:

CKLF-like MARVEl transmembrane domain containing 4

CRC:

Colorectal cancer

CSO-SA:

Curcumin encapsulated in stearic acid g-chitosan oligosaccharide

DBD:

DNA binding domain

dODNs:

Decoy oligodeoxynucleotides

EGFR:

Epidermal growth factor receptor

ERK:

Extracellular signal regulated kinases

FAK:

Focal adhesion kinase

FGF:

Fibroblast growth factor

FOLFOX:

5-Fluorouracil, leucovorin and oxaliplatin

GPCRs:

G-protein coupled receptors

JAK:

Janus kinase

MMP:

Matrix metalloproteinases

NTD:

N-terminal domain

PDB:

Protein Data Bank

PDGF:

Platelet derived growth factor

PIAS:

Protein inhibitor of activated STAT

P-STAT3:

Phosphorylated STAT3

ROS:

Reactive oxygen species

RT:

Radiotherapy

SH2:

Src homology

SOCS:

Suppressors of cytokine signaling

STAT:

Signal transducers and activators of transcription

TF:

Transcription factors

TME:

Tumor microenvironment

TNBS:

2,4,6- Trinitrobenzene sulfonic acid

TLRs:

Toll like receptors

VEGF:

Vascular endothelial growth factor

WHO:

World health organization

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Acknowledgements

This work was supported by Inha University Research Grant.

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  1. Gayathri Chalikonda and Hoomin Lee have Equally contributed.

Authors and Affiliations

  1. Internal Medicine, University of Nevada, Reno, NV-89502, USA

    Gayathri Chalikonda

  2. NanoBio High-Tech Materials Research Center, Department of Biological Engineering, Inha University, Incheon, 22212, Republic of Korea

    Hoomin Lee, Aliya Sheik & Yun Suk Huh

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  1. Gayathri Chalikonda
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Chalikonda, G., Lee, H., Sheik, A. et al. Targeting key transcriptional factor STAT3 in colorectal cancer. Mol Cell Biochem 476, 3219–3228 (2021). https://doi.org/10.1007/s11010-021-04156-8

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