Involvement of abnormal dystroglycan expression and matriglycan levels in cancer pathogenesis

Cancer Cell International

Review

Àngels Pastor¹  Cristina Quereda¹  José Martín-Nieto² 

[1] Departamento de Fisiología, Genética y Microbiología, Facultad de Ciencias, Universidad de Alicante, P.O. Box 99, Campus Universitario San Vicente, 03080, Alicante, Spain;Departamento de Fisiología, Genética y Microbiología, Facultad de Ciencias, Universidad de Alicante, P.O. Box 99, Campus Universitario San Vicente, 03080, Alicante, Spain;Instituto Multidisciplinar para el Estudio del Medio ‘Ramón Margalef’, Universidad de Alicante, 03080, Alicante, Spain;

关键词: Dystroglycan;    Cancer;    Tumorigenesis;    Glycosylation;    Gene expression;    Signal transduction;   

DOI  :  10.1186/s12935-022-02812-7

 received in 2022-08-24, accepted in 2022-11-28,  发布年份 2022

来源: Springer

【 摘 要 】

Dystroglycan (DG) is a glycoprotein composed of two subunits that remain non-covalently bound at the plasma membrane: α-DG, which is extracellular and heavily O-mannosyl glycosylated, and β-DG, an integral transmembrane polypeptide. α-DG is involved in the maintenance of tissue integrity and function in the adult, providing an O-glycosylation-dependent link for cells to their extracellular matrix. β-DG in turn contacts the cytoskeleton via dystrophin and participates in a variety of pathways transmitting extracellular signals to the nucleus. Increasing evidence exists of a pivotal role of DG in the modulation of normal cellular proliferation. In this context, deficiencies in DG glycosylation levels, in particular those affecting the so-called matriglycan structure, have been found in an ample variety of human tumors and cancer-derived cell lines. This occurs together with an underexpression of the DAG1 mRNA and/or its α-DG (core) polypeptide product or, more frequently, with a downregulation of β-DG protein levels. These changes are in general accompanied in tumor cells by a low expression of genes involved in the last steps of the α-DG O-mannosyl glycosylation pathway, namely POMT1/2, POMGNT2, CRPPA, B4GAT1 and LARGE1/2. On the other hand, a series of other genes acting earlier in this pathway are overexpressed in tumor cells, namely DOLK, DPM1/2/3, POMGNT1, B3GALNT2, POMK and FKTN, hence exerting instead a pro-oncogenic role. Finally, downregulation of β-DG, altered β-DG processing and/or impaired β-DG nuclear levels are increasingly found in human tumors and cell lines. It follows that DG itself, particular genes/proteins involved in its glycosylation and/or their interactors in the cell could be useful as biomarkers of certain types of human cancer, and/or as molecular targets of new therapies addressing these neoplasms.

【 授权许可】

CC BY   
© The Author(s) 2022

【 图 表 】

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Fig. 1