Role of Tumor Suppressor PTEN and Its Regulation in Malignant Transformation of Endometrium

• Published in: Biochemistry (Moscow) Vol. 87; no. 11; pp. 1310 - 1326
• Main Authors: Perevalova, Alina M., Kobelev, Vyacheslav S., Sisakyan, Virab G., Gulyaeva, Lyudmila F., Pustylnyak, Vladimir O.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01.11.2022; Springer; Springer Nature B.V
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Cell Transformation, Neoplastic - genetics; Cytoplasm; Development and progression; Endometrial cancer; Endometrial Neoplasms - genetics; Endometrial Neoplasms - metabolism; Endometrial Neoplasms - pathology; Endometrium; Female; Genes, Tumor Suppressor; Genetic aspects; Humans; Identification and classification; Life Sciences; Microbiology; Phosphatidylinositol 3-Kinases - metabolism; Properties; Proto-Oncogene Proteins c-akt - metabolism; PTEN Phosphohydrolase - metabolism; PTEN protein; Regulatory mechanisms (biology); Review; Signal Transduction; Structure; Substrates; Tumor suppressor genes; Tumors; Russia; PTEN; endometrial cancer; endometrial hyperplasia; gene regulation
• ISSN: 0006-2979; 1608-3040
• DOI: 10.1134/S0006297922110104

Tumor-suppressive effects of PTEN are well-known, but modern evidence suggest that they are not limited to its ability to inhibit pro-oncogenic PI3K/AKT signaling pathway. Features of PTEN structure facilitate its interaction with substrates of different nature and display its activity in various ways both in the cytoplasm and in cell nuclei, which makes it possible to take a broader look at its ability to suppress tumor growth. The possible mechanisms of the loss of PTEN effects are also diverse – PTEN can be regulated at many levels, leading to change in the protein activity or its amount in the cell, while their significance for the development of malignant tumors has yet to be studied. Here we summarize the current data on the PTEN structure, its functions and changes in its regulatory mechanisms during malignant transformation of the cells, focusing on one of the most sensitive to the loss of PTEN types of malignant tumors – endometrial cancer.