The Role of Phosphatidylinositol 3-Kinase Catalytic Subunit Type 3 in the Pathogenesis of Human Cancer.

Abstract

Phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3), the mammalian ortholog of yeast vesicular protein sorting 34 (Vps34), belongs to the phosphoinositide 3-kinase (PI3K) family. PIK3C3 can phosphorylate phosphatidylinositol (PtdIns) to generate phosphatidylinositol 3-phosphate (PI3P), a phospholipid central to autophagy. Inhibition of PIK3C3 successfully inhibits autophagy. Autophagy maintains cell survival when modifications occur in the cellular environment and helps tumor cells resist metabolic stress and cancer treatment. In addition, PIK3C3 could induce oncogenic transformation and enhance tumor cell proliferation, growth, and invasion through mechanisms independent of autophagy. This review addresses the structural and functional features, tissue distribution, and expression pattern of PIK3C3 in a variety of human tumors and highlights the underlying mechanisms involved in carcinogenesis. The implications in cancer biology, patient prognosis prediction, and cancer therapy are discussed. Altogether, the discovery of pharmacological inhibitors of PIK3C3 could reveal novel strategies for improving treatment outcomes for PIK3C3-mediated human diseases.

• Authors: Chien-An Chu, Yi-Wen Wang, Yi-Lin Chen, Hui-Wen Chen, Jing-Jing Chuang, Hong-Yi Chang, Chung-Liang Ho, Chen Chang, Nan-Haw Chow, Chung-Ta Lee
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 20 (Oct 11 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 34681622 (Publication Type: Journal Article, Review)

Chemical References

• Class III Phosphatidylinositol 3-Kinases

Topics

• Autophagy
• Cell Proliferation
• Class III Phosphatidylinositol 3-Kinases (antagonists & inhibitors, genetics, metabolism)
• Disease Progression
• Gene Expression Regulation, Neoplastic
• Humans
• Neoplasms (metabolism, pathology)
• Neoplastic Stem Cells (cytology, metabolism)
• Protein Domains