Role of PFKFB3 and PFKFB4 in Cancer: Genetic Basis, Impact on Disease Development/Progression, and Potential as Therapeutic Targets
Department of Histology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland
Department of Pathology, Pomeranian Medical University, 71-252 Szczecin, Poland
Department of Genetics, Wroclaw Medical University, 50-368 Wroclaw, Poland
Department of Biochemical Engineering, Wroclaw University of Science and Technology, 50-370 Wroclaw, Poland
Laboratoire de physique et chimie théoriques, Université de Lorraine, F-54000 Nancy, France
Department of Biomedical and Clinical Sciences (BKV), Division of Cell Biology, Linköping University, Region Östergötland, 581 85 Linköping, Sweden
Department of Otorhinolaryngology in Linköping, Anesthetics, Operations and Specialty Surgery Center, Region Östergötland, 581 85 Linköping, Sweden
Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, Canada
Research Institute in Oncology and Hematology, Cancer Care Manitoba, University of Manitoba, Winnipeg, MB R3E 0V9, Canada
Department of Physiotherapy, Wroclaw University School of Physical Education, 51-612 Wroclaw, Poland
Authors to whom correspondence should be addressed.
Academic Editors: Lingzhi Wang and Qiang Jeremy Wen
Received: 7 January 2021 / Revised: 12 February 2021 / Accepted: 14 February 2021 / Published: 22 February 2021
Recently, our understanding of PFK-2 isozymes, particularly with regards to their roles in cancer, has developed significantly. This review aims to compile the most crucial achievements in this field. Due to the prevailing number of recent studies on PFKFB3 and PFKFB4, we mainly focused on these two isozymes. Here, we comprehensively describe the discoveries and observations to date related to the genetic basis, regulation of expression, and protein structure of PFKFB3/4 and discuss the functional involvement in tumor progression, metastasis, angiogenesis, and autophagy. Furthermore, we highlight crucial studies on targeting PFKFB3 and PFKFB4 for future cancer therapy. This review offers a cutting-edge condensed outline of the significance of specific PFK-2 isozymes in malignancies and can be helpful in understanding past discoveries and planning novel research in this field.