Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Integrins Within the Tumor Microenvironment: Biological Functions and Advances in Therapeutic Targeting

Version 1 : Received: 30 November 2020 / Approved: 1 December 2020 / Online: 1 December 2020 (18:26:11 CET)

A peer-reviewed article of this Preprint also exists.

Kevin Dzobo.OMICS: A Journal of Integrative Biology.ahead of printhttp://doi.org/10.1089/omi.2021.0069 Kevin Dzobo.OMICS: A Journal of Integrative Biology.ahead of printhttp://doi.org/10.1089/omi.2021.0069

Journal reference: OMICS: A Journal of Integrative Biology 2021
DOI: 10.1089/omi.2021.0069

Abstract

Many cellular functions important for tumor initiation and progression are mediated by members of the integrin family, a diverse family of cell adhesion receptors. With recent studies emphasising on the role of the tumor microenvironment (TME) in tumor initiation and progression, it is not surprising that a lot of attention is being given to integrins. Several integrins are under trial with many demonstrating appealing activity in patients with different cancers. A deeper knowledge of the functions of integrins within the tumor microenvironment is still required, and might lead to better inhibitors being discovered. Integrin expression is commonly dysregulated in many tumors with integrins playing key roles in signaling as well as promotion of tumor cell invasion and migration. This review report new data on the differential expression of integrins within solid tumors using two publicly available resources: The Cancer Genomic Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA). In this analysis, I investigated the expression of integrin alpha 2 (ITGα2), ITGα3, ITGβ4 and ITGβ6 in tumor tissues versus adjacent normal tissues. This analysis showed that integrins were differentially expressed in cervical squamous cell carcinoma (CESC), head and neck squamous cell carcinoma (HNSC), esophageal carcinoma (ESCA) and lung adenocarcinoma (LUAD). This analysis showed that ITGα2 and ITGβ6 expression are upregulated in CESC and ESCA, ITGα3 is upregulated in HNSC and ESCA whilst ITGβ4 is highly expressed in CESC, HNSC, ESCA and LUAD tumor tissues compared to adjacent normal tissues. Integrins also play a major role in adhesion of circulating tumor cells to new sites and the resulting formation of secondary tumors. Furthermore, integrins have demonstrated the ability to promoting stem cell-like properties in tumor cells as well as drug resistance. Anti-integrin therapies rely heavily on the doses or concentrations used as these determine whether the drugs act as antagonists or as integrin agonists. This review offers the latest synthesis in terms of current knowledge of integrins functions within the tumor microenvironment and potential targets for different cancers.

Subject Areas

Integrins; Tumor Microenvironment; Drug Resistance; Migration; Metastasis; Solid Tumors; The Cancer Genome Atlas; Gene Expression; Computational Biology; Therapeutic Targeting

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