Intertwining of Activin A and TGFβ Signaling: Dual Roles in Cancer Progression and Cancer Cell Invasion.
Intertwining of Activin A and TGFβ Signaling: Dual Roles in Cancer Progression and Cancer Cell Invasion.
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DOI：
10.3390/cancers7010070
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发表时间：
2014-12-30
期刊：
影响因子：
5.2
通讯作者：
Andl CD
中科院分区：
文献类型：
--
作者：
Loomans HA;Andl CD
近年来，大量研究探讨了激活素 A 在癌症中具有争议的作用。激活素 A 是转化生长因子 β (TGFβ) 超家族的成员，其在胚胎发生过程中中胚层细胞命运分化和繁殖过程中的功能得到了最好的表征。在胚胎发生过程中，TGFβ 超家族配体、TGFβ、骨形态发生蛋白 (BMP) 和激活素充当有效的形态发生素。与 TGFβ 和 BMP 类似，激活素 A 是一种在早期胚胎发生过程中高度系统表达的蛋白质；然而，出生后表达总体减少，并仍处于严格的时空调控之下。重要的是，激活素 A 的正常产后表达与各种免疫细胞类型以及子宫内膜细胞的迁移和侵袭特性有关。发育过程中异常的激活素 A 信号传导会导致显着的形态缺陷和过早死亡。有趣的是，已发现激活素 A 在癌症中具有致癌作用和抑癌作用。对激活素 A 在前列腺癌和乳腺癌中作用的研究已证明其具有肿瘤抑制作用，而在肺癌和头颈鳞状细胞癌中，一致表明激活素 A 表达与增殖、侵袭增加和患者预后不良相关。激活素 A 信号传导具有高度的背景依赖性，这一点在上皮细胞肿瘤和微环境的研究中得到了证明。这篇综述讨论了正常激活素 A 信号传导与 TGFβ 的比较，并强调了其失调如何导致癌症进展和细胞侵袭。
In recent years, a significant amount of research has examined the controversial role of activin A in cancer. Activin A, a member of the transforming growth factor β (TGFβ) superfamily, is best characterized for its function during embryogenesis in mesoderm cell fate differentiation and reproduction. During embryogenesis, TGFβ superfamily ligands, TGFβ, bone morphogenic proteins (BMPs) and activins, act as potent morphogens. Similar to TGFβs and BMPs, activin A is a protein that is highly systemically expressed during early embryogenesis; however, post-natal expression is overall reduced and remains under strict spatiotemporal regulation. Of importance, normal post-natal expression of activin A has been implicated in the migration and invasive properties of various immune cell types, as well as endometrial cells. Aberrant activin A signaling during development results in significant morphological defects and premature mortality. Interestingly, activin A has been found to have both oncogenic and tumor suppressor roles in cancer. Investigations into the role of activin A in prostate and breast cancer has demonstrated tumor suppressive effects, while in lung and head and neck squamous cell carcinoma, it has been consistently shown that activin A expression is correlated with increased proliferation, invasion and poor patient prognosis. Activin A signaling is highly context-dependent, which is demonstrated in studies of epithelial cell tumors and the microenvironment. This review discusses normal activin A signaling in comparison to TGFβ and highlights how its dysregulation contributes to cancer progression and cell invasion.
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