Department of Pediatrics, Darby Children's Research Institute, Medical University of South Carolina, Charleston, SC 29425, USA.
Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.
Biomolecules. 2023 Jan 30;13(2):259. doi: 10.3390/biom13020259.
() encodes a tumor-suppressive phosphatase with both lipid and protein phosphatase activity. The tumor-suppressive functions of PTEN are lost through a variety of mechanisms across a wide spectrum of human malignancies, including several rare cancers that affect pediatric and adult populations. Originally discovered and characterized as a negative regulator of the cytoplasmic, pro-oncogenic phosphoinositide-3-kinase (PI3K) pathway, PTEN is also localized to the nucleus where it can exert tumor-suppressive functions in a PI3K pathway-independent manner. Cancers can usurp the tumor-suppressive functions of PTEN to promote oncogenesis by disrupting homeostatic subcellular PTEN localization. The objective of this review is to describe the changes seen in PTEN subcellular localization during tumorigenesis, how PTEN enters the nucleus, and the spectrum of impacts and consequences arising from disrupted PTEN nuclear localization on tumor promotion. This review will highlight the immediate need in understanding not only the cytoplasmic but also the nuclear functions of PTEN to gain more complete insights into how important PTEN is in preventing human cancers.
() 编码一种具有脂质和蛋白磷酸酶活性的肿瘤抑制磷酸酶。PTEN 的肿瘤抑制功能通过多种机制在广泛的人类恶性肿瘤中丧失，包括几种影响儿童和成人的罕见癌症。PTEN 最初被发现并被表征为细胞质原癌性磷酸肌醇-3-激酶 (PI3K) 途径的负调节剂，也定位于细胞核，在那里它可以以 PI3K 途径非依赖性方式发挥肿瘤抑制功能。癌症可以通过破坏细胞内稳态的 PTEN 定位来篡夺 PTEN 的肿瘤抑制功能，从而促进肿瘤发生。本综述的目的是描述肿瘤发生过程中 PTEN 亚细胞定位的变化，PTEN 如何进入细胞核，以及破坏 PTEN 核定位对肿瘤促进产生的一系列影响和后果。本综述将强调不仅要了解细胞质功能，还要了解核内功能的迫切需要，以更全面地了解 PTEN 在预防人类癌症中的重要性。
