Desmoglein-2 as a cancer modulator: friend or foe?

Kay K Myo Min; Charlie B Ffrench; Barbara J McClure; Michael Ortiz; Emma L Dorward; Michael S Samuel; Lisa M Ebert; Mỹ G Mahoney; Claudine S Bonder

doi:10.3389/fonc.2023.1327478

Desmoglein-2 as a cancer modulator: friend or foe?

Front Oncol. 2023 Dec 22:13:1327478. doi: 10.3389/fonc.2023.1327478. eCollection 2023.

Authors

Kay K Myo Min^#¹, Charlie B Ffrench^#¹, Barbara J McClure^{1

2}, Michael Ortiz¹, Emma L Dorward¹, Michael S Samuel^{1

2

3}, Lisa M Ebert^{1

4}, Mỹ G Mahoney⁵, Claudine S Bonder^{1

2}

Affiliations

¹ Centre for Cancer Biology, SA Pathology and the University of South Australia, Adelaide, SA, Australia.
² Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia.
³ Basil Hetzel Institute, Queen Elizabeth Hospital, SA, Adelaide, Australia.
⁴ Royal Adelaide Hospital, Adelaide, SA, Australia.
⁵ Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University, Philadelphia, PA, United States.

^# Contributed equally.

Abstract

Desmoglein-2 (DSG2) is a calcium-binding single pass transmembrane glycoprotein and a member of the large cadherin family. Until recently, DSG2 was thought to only function as a cell adhesion protein embedded within desmosome junctions designed to enable cells to better tolerate mechanical stress. However, additional roles for DSG2 outside of desmosomes are continuing to emerge, particularly in cancer. Herein, we review the current literature on DSG2 in cancer and detail its impact on biological functions such as cell adhesion, proliferation, migration, invasion, intracellular signaling, extracellular vesicle release and vasculogenic mimicry. An increased understanding of the diverse repertoire of the biological functions of DSG2 holds promise to exploit this cell surface protein as a potential prognostic biomarker and/or target for better patient outcomes. This review explores the canonical and non-canonical functions of DSG2, as well as the context-dependent impacts of DSG2 in the realm of cancer.

Keywords: cadherin; cancer; desmoglein-2 (DSG2); intercellular junctions; non-canonical role; prognostic biomarker; vasculogenic mimicry.

Publication types

Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This review was supported by grants to CB: a Tour de Cure (Pioneering Grant RSP-358-2020), Cancer Council SA (Beat Cancer Project Support GNT2013221) and NHMRC (GNT2021009 & GNT2013460). KM, CF and MO were supported by a RTP/USAPA post-graduate scholarship. CF was also supported by the Australian Rotary Health and Phillip & Glenis Hayes PhD scholarship.