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TFCP2 as a therapeutic nexus: unveiling molecular signatures in cancer

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Abstract

Tumor suppressor genes and proto-oncogenes comprise most of the complex genomic landscape associated with cancer, with a minimal number of genes exhibiting dual-context-dependent functions. The transcription factor cellular promoter 2 (TFCP2), a pivotal transcription factor encoded by the alpha globin transcription factor CP2 gene, is a constituent of the TFCP2/grainyhead family of transcription factors. While grainyhead members have been extensively studied for their crucial roles in developmental processes, embryogenesis, and multiple cancers, the TFCP2 subfamily has been relatively less explored. The molecular mechanisms underlying TFCP2's involvement in carcinogenesis are still unclear even though it is a desirable target for cancer treatment and a therapeutic marker. This comprehensive literature review summarizes the molecular functions of TFCP2, emphasizing its involvement in cancer pathophysiology, particularly in the epithelial-mesenchymal transition and metastasis. It highlights TFCP2's critical function as a regulatory target and explores its potential as a prognostic marker for survival and inflammation in carcinomas. Its ambiguous association with carcinomas underlines the urgent need for an in-depth understanding to facilitate the development of more efficacious targeted therapeutic modality and diagnostic tools. This study aims to elucidate the multifaceted effects of TFCP2 regulation, through a comprehensive integration of the existing knowledge in cancer therapeutics. Furthermore, the clinical relevance and the inherent challenges encountered in investigating its intricate role in cancer pathogenesis have been discussed in this review.

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Data availability

All data has been included in the manuscript. If required, it can be available from the corresponding author upon reasonable request.

Abbreviations

TFCP2:

Transcription factor CP2

TFCP2L1:

Transcription factor CP2 like 1

UBP1:

Upstream Binding Protein 1

DBD:

DNA binding domains

GRH:

Grainyhead family

SAM:

Sterile alpha motif

DAPK:

Death-associated protein kinase

NF-E2:

Nuclear Factor, Erythroid 2

HIV:

Human immunodeficiency virus

(hESCs)/ESCs:

Embryonic stem cells

GRHL :

Grainyhead like

HCC:

Hepatocellular carcinoma

YY1:

Yin-Yang 1

CYP11A1:

Cytochrome P450 family 11 subfamily A member 1

CPEB1:

Cytoplasmic Polyadenylation Element Binding Protein 1

CRC:

Colorectal cancer

ASIC2:

Acid-sensing ion channel subunit 2

miR:

MiRNA

circITCH:

Circular RNA Itchy E3 Ubiquitin Protein Ligase

YAP1:

Yes1 Associated Transcriptional Regulator

DAPK:

Death-associated protein kinase

TS:

Thymidylate synthase

TFCP2dn:

Dominant-negative TFCP2

SCC:

Squamous cell carcinoma

TCF:

T cell factor

EMT:

Epithelial-Mesenchymal Transition

AKT:

AKT Serine/Threonine Kinase

ChIP:

Chromatin immunoprecipitation

ECM:

Extracellular matrix

VEGF:

Vascular Endothelial Growth Factor A

MMPs:

Matrix Metallopeptidase

IL-8:

Interleukin

5-FU:

5-Fluorouracil

AEG-1:

Astrocyte Elevated Gene-1

CSCs:

Cancer stem cells

MET:

Mesenchymal-to-epithelial transition

GRP78:

Glucose-regulated protein

NOTCH1:

Neurogenic locus notch homolog protein 1

DNMT1:

DNA (cytosine-5)-methyltransferase 1

FQl1:

Factor quinolinone inhibitor 1

OPN:

Osteopontin

TJP1:

Tight junction protein 1

CCT3:

Chaperonin containing TCP1 subunit 3

YAP:

Yes associated transcriptional regulator

YY1:

Yin yang 1 transcription factor

TCF:

T cell factor

SREBP2:

Sterol regulatory element binding transcription factor 2

TGF-β:

Transforming growth factor β

PI3K:

Phosphoinositide 3-kinases

EGFR:

Epidermal growth factor receptor

SMAD2:

SMAD family member 2

SULF1:

Sulfatase 1

EWSR1:

EWS RNA binding protein 1

FUS:

FUS RNA binding protein

MAGE-A11:

Melanoma-associated antigen 11

ZEB1:

Zinc finger E-Box binding homeobox 1

TSG101:

Tumor susceptibility gene 101

ATF3:

Activating transcription factor 3

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Funding

This research was funded by the National Research Foundation (NRF) of Korea, funded by the Korean government (2021R1C1C1013875, 2021R1A6A1A03038785, 2021R1F1A1055694).

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  1. Neha Kaushik and Apurva Jaiswal-these authors contributed equally.

Authors and Affiliations

  1. Department of Biotechnology, College of Engineering, The University of Suwon, Hwaseong, 18323, Korea

    Neha Kaushik & Pradeep Bhartiya

  2. Plasma Bioscience Research Center/Department of Electrical and Biological Physics, Kwangwoon University, Seoul, 01897, Korea

    Apurva Jaiswal, Eun Ha Choi & Nagendra Kumar Kaushik

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  1. Neha Kaushik
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Conceptualization: NK; writing original draft: NK, AJ, and PB; writing, review, and editing: NK and AJ; funding acquisition: NK, NKK, and EHC; supervision: NKK and EHC. All authors have read and agreed to the published version of the manuscript.

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Kaushik, N., Jaiswal, A., Bhartiya, P. et al. TFCP2 as a therapeutic nexus: unveiling molecular signatures in cancer. Cancer Metastasis Rev (2024). https://doi.org/10.1007/s10555-024-10175-w

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