Lefler Julia E, Seward Cara, Ostrowski Michael C
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, United States; Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, United States.
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, United States; Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, United States.
Adv Cancer Res. 2022;154:203-226. doi: 10.1016/bs.acr.2022.01.002. Epub 2022 Mar 18.
Decades of research have concluded that disruptions to Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) have profound effects on cancer progression. However, as our understanding of the tumor stroma has evolved, we can appreciate that disruptions to tumor suppressors such as PTEN should not be studied solely in an epithelial context. Inactivation of PTEN in the stroma is associated with worse outcomes in human cancers, therefore, it is important to understand activities regulated downstream of PTEN in stromal compartments. Studies reviewed herein provide evidence for important mechanistic targets downstream of PTEN signaling in cancer-associated fibroblasts (CAFs), a major component of the tumor stroma. We also discuss the potential clinical implications for these findings.
数十年的研究得出结论,10号染色体缺失的磷酸酶和张力蛋白同源物(PTEN)的破坏对癌症进展具有深远影响。然而,随着我们对肿瘤基质的理解不断发展,我们认识到,诸如PTEN等肿瘤抑制因子的破坏不应仅在上皮环境中进行研究。基质中PTEN的失活与人类癌症的更差预后相关,因此,了解PTEN在基质区室下游调控的活性非常重要。本文综述的研究为肿瘤相关成纤维细胞(CAFs)(肿瘤基质的主要成分)中PTEN信号下游的重要机制靶点提供了证据。我们还讨论了这些发现的潜在临床意义。