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Kinases and therapeutics in pathogen mediated gastric cancer

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Abstract

Introduction

Many pathogens have coexisted with humans for millennia and can cause chronic inflammation which is the cause of gastritis. Gastric cancer (GC) is associated with 8.8% of cancer related deaths, making it one of the leading causes of cancer related deaths worldwide. This review is intended to give brief information about Helicobacter pylori (H. pylori), Epstein–Barr virus (EBV), human cytomegalovirus (HCMV) role in GC and associated kinases. These organisms can trigger multiple cellular pathways aiming for unnatural cellular proliferation, apoptosis, migration and inflammatory response. Kinases also can activate and deactivate the signalling leading to aforementioned pathways. Therefore, studying kinases is inevitable.

Material and methods

This review is the comprehensive collection of information from different data sources such as journals, book, book chapters and verified online information.

Conclusion

Kinase amplifications could be used as diagnostic, prognostic, and predictive biomarkers in various cancer types. Hence targeting kinase and related signalling molecules could be considered as a potential approach to prevent cancer through these organisms. Here we summarize the brief information about the role of kinases, signalling and their therapeutics in GC concerning H. pylori, EBV and HCMV.

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Abbreviations

ARID1A:

AT-rich interactive domain-containing protein 1A

Bcl-2:

B-Cell CLL/Lymphoma 2

BabA:

Blood group antigen binding adhesin A

cas-9:

Caspase-3 (cas-3), caspase-9

CCDC151:

Coiled-coil domain containing 151

CHRNB2:

Cholinergic receptor nicotinic beta 2 subunit

CIMP:

Concordant methylation of multiple genes/loci

CLTs:

Cytomegalovirus latency-associated transcripts

CagA:

Cytotoxin associated gene A

cagPAI:

Cytotoxin-associated genes pathogenicity island

COX-2:

Cyclooxygenase-2

CTLs:

Cytotoxic T cells

EBV:

Epstein–Barr virus

EBVaGC:

EBV-associated GC

EBNA-1:

EBV nuclear antigen-1

EPHA4:

EPH receptor A4

EGF:

Epidermal growth factor

ERBB2:

Erb-B2 receptor tyrosine kinase

ERBB4:

Receptor tyrosine-protein kinase erbB-4 precursor

ERK1/2:

Extracellular signal-regulated kinase ½

FGFR2:

Fibroblast growth factor receptor 2

leb:

Fucosylated lewisb

GC:

Gastric cancer

GMPR2:

Guanosine monophosphate reductase 2

HSP-70:

Heat shock protein-70

H. pylori :

Helicobacter pylori

HDGFRP2:

Hepatoma-derived growth factor-related protein 2 isoform 1

LMP:

Latent membrane proteins

IAPs:

Inhibitors of apoptosis

HCMV:

Human cytomegalovirus

HER2:

Human Epidermal growth factor Receptor 2

IHH:

Indian hedgehog homolog

ITK:

Inducible T-cell KINASE

IARC:

International Agency for Research on Cancer

AP-1:

Jun/Activator protein 1

mTOR:

Mammalian target of rapamycin

MMPs:

Matrix metalloproteases

Met:

Mesenchymal-epithelial transition factor

MLH1:

MutL Homolog 1

nRTK:

Non-receptor tyrosine kinases

NFκB:

Nuclear Factor kappa-light-chain-enhancer of activated B cells

PAK1:

P21 (RAC1) Activated Kinase 1

PAK2:

PAK2 Gene—P21 (RAC1) Activated Kinase 2

PLCγ:

Phospholipase Cγ

PTEN:

Phosphatase and Tensin Homolog

PIK3CA:

Phosphatidylinositol 4,5-bisphosphate 3-Kinase Catalytic subunit Alpha isoform

PI3K:

Phosphatidylinositol 3-Kinase/Akt

PD-1:

Programmed cell death 1

PGE2:

Prostaglandin E2

PML:

Progressive multifocal leukoencephalopathy

Src:

Proto-oncogene tyrosine-protein kinase

RTK:

Receptor tyrosine kinases

RPTP:

Receptor protein tyrosine phosphatase

MEK:

Ras/Raf/Mitogen-activated protein kinase/ERK kinase

ERK:

Extracellular-signal-regulated kinase

SSTR1:

Somatostatin Receptor 1

SHP2:

Src homology region 2

STAD:

Stomach adenocarcinoma

TYK2:

Tyrosine kinase 2

VacA:

Vacuolating Cytotoxin A

VSTM2L:

V-set and transmembrane domain containing 2 like

VEGFR:

VEGF receptor

HAUSP:

Ubiquitin-specific protease USP7

ZEB1:

Zinc finger E-box-binding homeobox 1

TP53:

Tumour protein P53

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Acknowledgements

This project was supported by Council of Scientific and Industrial Research Grant no. 37(1693)/17/EMR-II and Department of Science and Technology as Ramanujan fellowship grant no. SB/S2/RJN-132/20/5. DST-EMR: EMR/2017/001637.We are thankful to the Council of Scientific and Industrial Research and DST-Inspire for fellowship to Charu Sonkar and Nidhi Varshney respectively. The funding organization has not played any role in the study design or preparation of the manuscript. We appreciate our lab colleagues for insightful discussions and advice. We gratefully acknowledge the Indian Institute of Technology Indore for providing facilities and support. We further gratefully acknowledge Dr. Fabiola Ribeiro of Department of Biochemistry and Immunology, UFMG, Brazil for her efforts in correcting the language of the manuscript.

Funding

This project was supported by Council of Scientific and Industrial Research Grant no. 37(1693)/17/EMR-II and Department of Science and Technology as Ramanujan fellowship grant no. SB/S2/RJN-132/20/5. DST-EMR: EMR/2017/001637. We are thankful to the Council of Scientific and Industrial Research and DST-Inspire for fellowship to Charu Sonkar and Nidhi Varshney respectively. The funding organization has not played any role in the study design or preparation of the manuscript.

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  1. Infectious Bioengineering Lab, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, Madhya Pradesh, 453552, India

    Charu Sonkar, Nidhi Varshney & Hem Chandra Jha

  2. Central for Advanced Research, SVIMS, Tirupathi and Omicron laboratories, Vijaywada, India

    Siva Koganti

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  1. Charu Sonkar
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  2. Nidhi Varshney
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  4. Hem Chandra Jha
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Correspondence to Hem Chandra Jha.

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Sonkar, C., Varshney, N., Koganti, S. et al. Kinases and therapeutics in pathogen mediated gastric cancer. Mol Biol Rep 49, 2519–2530 (2022). https://doi.org/10.1007/s11033-021-07063-9

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