Regulation of the tumour suppressor PTEN by phosphorylation and oligomerization

肿瘤抑制因子PTEN是一种参与控制细胞生长、细胞死亡和细胞迁移的酶。PTEN被认为是一种肿瘤抑制基因，因为许多肿瘤细胞都被发现携带PTEN基因突变，导致PTEN蛋白丢失或PTEN酶活性丧失。PTEN基因的遗传突变是一种罕见的遗传性疾病考登病的原因。考登病患者易患皮肤癌、甲状腺癌和乳腺癌。在实验室条件下，增加肿瘤细胞中PTEN的丰度可以抑制它们的生长，从而发挥肿瘤抑制因子的作用。除了作为肿瘤抑制因子外，PTEN还控制癌细胞的扩散。虽然对PTEN参与肿瘤形成和癌细胞扩散的研究很多，但对PTEN如何抑制肿瘤细胞的生长和扩散还不完全清楚。PTEN的酶活性增强了蛋白质中名为磷酸的化学基团和细胞膜中名为磷脂的脂溶化合物的去除。PTEN抑制细胞生长和扩散的能力是由于其酶活性所致。然而，PTEN的酶活性是如何调节的还不是很清楚。为了使PTEN能有效地促进特定细胞蛋白和磷脂中磷酸基团的去除，PTEN需要位于这些蛋白和磷脂附近。然而，PTEN如何移动到这些蛋白质和磷脂存在的位置仍然是未知的。这项建议旨在研究PTEN酶在细胞内的活性和运动的调节。拟议的研究结果将为PTEN基因突变如何促进癌症的形成和癌细胞的扩散提供新的线索，并可能促进癌症治愈的探索。

The tumour suppressor PTEN is an enzyme involved in controlling cell growth, cell death, and cell migration. PTEN was identified as a tumour suppressor because many tumour cells were found to carry mutations in the PTEN gene that cause the loss of PTEN protein or the loss of PTEN enzyme activity. Hereditary mutations of the PTEN gene are the causes of a rare genetic disease called Cowden's disease. Cowden's disease patients are predisposed to developing skin, thyroid, and breast cancers. In laboratory conditions, increasing the abundance of PTEN in tumour cells such as brain and prostate tumour cells can suppress their growth, hence its role as a tumour suppressor. In addition to its role as a tumour suppressor, PTEN controls cancer cell spreading. Although much is known about the involvement of PTEN in cancer formation and the spreading of cancer cells, how PTEN suppresses tumour cell growth and spreading is not fully understood. The enzyme activity of PTEN enhances the removal of a chemical group called phosphate group from proteins and the fat-soluble compounds called phospholipids in the cell membrane. The ability of PTEN to suppress cell growth and spreading is due to its enzyme activity. However, exactly how the enzyme activity of PTEN is regulated is not well understood. In order for PTEN to efficiently enhance the removal of phosphate group from specific cellular proteins and phospholipids, PTEN needs to be located in close vicinity to these proteins and phospholipids. However, exactly how PTEN moves to the locations where these proteins and phospholipids are present remains elusive. This proposal aims at studying the regulation of PTEN enzyme activity and movement inside the cells. Results of the proposed studies will shed new light on how PTEN gene mutations contribute to cancer formation and the spreading of cancer cells and may facilitate the search for the cure of cancers.