Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.
Aging Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, 15261, USA.
Cancer Metastasis Rev. 2020 Jun;39(2):397-414. doi: 10.1007/s10555-020-09875-w.
Cellular senescence is a feature of most somatic cells. It is characterized by an irreversible cell cycle arrest and by the ability to secrete a plethora of mediators of inflammation and growth factors, which can alter the senescent cell's microenvironment. Senescent cells accumulate in tissues over time and contribute to both aging and the development of age-associated diseases. Senescent cells have antagonistic pleiotropic roles in cancer. Given the inability of senescent cells to proliferate, cellular senescence is a powerful tumor suppressor mechanism in young individuals. However, accumulation of senescent stromal cells during aging can fuel cancer cell growth in virtue of their capacity to release factors that stimulate cell proliferation. Caveolin-1 is a structural protein component of caveolae, invaginations of the plasma membrane involved in a variety of cellular processes, including signal transduction. Mounting evidence over the last 10-15 years has demonstrated a central role of caveolin-1 in the development of a senescent phenotype and the regulation of both the anti-tumorigenic and pro-tumorigenic properties of cellular senescence. In this review, we discuss the cellular mechanisms and functions of caveolin-1 in the context of cellular senescence and their relevance to the biology of cancer.
细胞衰老(cellular senescence)是大多数体细胞的特征。其特点是细胞周期不可逆停滞和分泌大量炎症和生长因子介质的能力,这可以改变衰老细胞的微环境。随着时间的推移,衰老细胞在组织中积累,并导致衰老和与年龄相关疾病的发展。衰老细胞在癌症中具有拮抗的多效性作用。鉴于衰老细胞不能增殖,细胞衰老在年轻人中是一种强大的肿瘤抑制机制。然而,衰老间质细胞的积累可以通过释放刺激细胞增殖的因子来为癌细胞生长提供动力。窖蛋白-1(caveolin-1)是质膜凹陷小窝(caveolae)的结构蛋白成分,参与多种细胞过程,包括信号转导。在过去的 10-15 年中,越来越多的证据表明窖蛋白-1在衰老表型的发展和细胞衰老的抗肿瘤和促肿瘤特性的调节中起着核心作用。在这篇综述中,我们讨论了窖蛋白-1在细胞衰老中的细胞机制和功能及其与癌症生物学的相关性。