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

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Abstract

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.

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Abbreviations

AH/EIN:

atypical hyperplasia/endometrial intraepithelial neoplasia

AKT:

protein kinase B, protein serine/threonine kinase family

BH:

benign hyperplasia

C2:

type II calcium-independent C2 domain

CTT:

carboxyl-terminal tail

EC:

endometrial cancer

PDZ-BM:

PDZ-binding motif

PIP3:

phosphatidylinositol-3,4,5-triphosphate

PTEN:

phosphatase and tensin homolog deleted on chromosome 10

TCGA:

The Cancer Genome Atlas

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Authors and Affiliations

  1. Novosibirsk State University, 630090, Novosibirsk, Russia

    Alina M. Perevalova, Lyudmila F. Gulyaeva & Vladimir O. Pustylnyak

  2. Federal Research Center of Fundamental and Translational Medicine, 630117, Novosibirsk, Russia

    Vyacheslav S. Kobelev, Lyudmila F. Gulyaeva & Vladimir O. Pustylnyak

  3. Novosibirsk Regional Oncology Center, 630108, Novosibirsk, Russia

    Virab G. Sisakyan

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  1. Alina M. Perevalova
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A. M. Perevalova, V. S. Kobelev, V. G. Sisakyan performed literature search and analysis; A. M. Perevalova wrote the manuscript; L. F. Gulyaeva and V. O. Pustylnyak edited the manuscript.

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Perevalova, A.M., Kobelev, V.S., Sisakyan, V.G. et al. Role of Tumor Suppressor PTEN and Its Regulation in Malignant Transformation of Endometrium. Biochemistry Moscow 87, 1310–1326 (2022). https://doi.org/10.1134/S0006297922110104

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