Regulation of Wnt Signaling Pathways at the Plasma Membrane and Their Misregulation in Cancer.
Regulation of Wnt Signaling Pathways at the Plasma Membrane and Their Misregulation in Cancer.
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Wnt信号通路在质膜上的调节及其在癌症中的失调。
DOI：
10.3389/fcell.2021.631623
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发表时间：
2021
影响因子：
5.5
通讯作者：
Ozhan G
中科院分区：
文献类型：
--
作者：
Azbazdar Y;Karabicici M;Erdal E;Ozhan G
Wnt信号传导是控制发育和稳态过程中的生长、分化和迁移等众多生理活动的关键信号传导途径之一。由于通路失调与包括恶性肿瘤在内的病理过程广泛相关，因此彻底了解通路调节对于开发有效的治疗方法至关重要。癌细胞的一个显着特征是它们的质膜组成和脂质组织与健康细胞显着不同。在这里，我们回顾了膜组成和脂质顺序通过严格调节 Wnt 受体复合物的形成和相互作用在 Wnt 信号通路激活中的关键作用。我们还详细讨论了 Wnt 通路的质膜成分，特别是配体、（共）受体和细胞外或膜结合调节剂在肺癌、结直肠癌、肝癌和乳腺癌中如何受到影响，这些癌症与 Wnt 信号传导的异常激活有关。 Wnt 受体复合体成分及其调节剂在这些癌症中经常错误表达，这似乎与转移和癌症进展相关。因此，质膜的组成和组织可用于开发新的抗癌药物，这些药物以高度特异性的方式靶向 Wnt 受体复合物，从而实现更有效的治疗结果。
Wnt signaling is one of the key signaling pathways that govern numerous physiological activities such as growth, differentiation and migration during development and homeostasis. As pathway misregulation has been extensively linked to pathological processes including malignant tumors, a thorough understanding of pathway regulation is essential for development of effective therapeutic approaches. A prominent feature of cancer cells is that they significantly differ from healthy cells with respect to their plasma membrane composition and lipid organization. Here, we review the key role of membrane composition and lipid order in activation of Wnt signaling pathway by tightly regulating formation and interactions of the Wnt-receptor complex. We also discuss in detail how plasma membrane components, in particular the ligands, (co)receptors and extracellular or membrane-bound modulators, of Wnt pathways are affected in lung, colorectal, liver and breast cancers that have been associated with abnormal activation of Wnt signaling. Wnt-receptor complex components and their modulators are frequently misexpressed in these cancers and this appears to correlate with metastasis and cancer progression. Thus, composition and organization of the plasma membrane can be exploited to develop new anticancer drugs that are targeted in a highly specific manner to the Wnt-receptor complex, rendering a more effective therapeutic outcome possible.
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影响因子：
16.6
作者：
Avgustinova A;Iravani M;Robertson D;Fearns A;Gao Q;Klingbeil P;Hanby AM;Speirs V;Sahai E;Calvo F;Isacke CM
通讯作者：
Isacke CM
影响因子：
11.2
作者：
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通讯作者：
Zhang W
影响因子：
5.6
作者：
Ali I;Medegan B;Braun DP
通讯作者：
Braun DP
影响因子：
4.8
作者：
Arcaro, Alexandre;Aubert, Muriel;Seckl, Michael J.
通讯作者：
Seckl, Michael J.
影响因子：
4.8
作者：
Brinkmann, Eva-Maria;Mattes, Benjamin;Oezbek, Suat
通讯作者：
Oezbek, Suat