CD133 蛋白是最常用的表面标记物之一，用于选择和识别具有干细胞样特征的癌细胞。然而，它的表达并不局限于肿瘤细胞；它还在各种正常组织的分化细胞和干/祖细胞中表达。 CD133 参与多种细胞过程，部分协调癌症中经常失调的重要途径的信号转导，例如 PI3K/Akt 信号传导和 Wnt/β-连环蛋白途径。 CD133 表达与癌症应激条件下增强的细胞自我更新、迁移、侵袭和存活相关。除了调节每种细胞类型中 CD133 表达的内在细胞机制外，周围环境的外在因素也会影响 CD33 水平。细胞中增强的 CD133 表达可以通过以上下文相关的方式放大特定信号通路的激活来赋予适应性优势。在这篇综述中，我们不仅描述了迄今为止已知的 CD133 生理功能，而且重要的是，我们分析了微环境变化如何影响 CD133 功能的调节，强调其作为癌症干细胞标记物之外的细胞适应性标记物的价值。© 2023。作者。

CD133 protein has been one of the most used surface markers to select and identify cancer cells with stem-like features. However, its expression is not restricted to tumoral cells; it is also expressed in differentiated cells and stem/progenitor cells in various normal tissues. CD133 participates in several cellular processes, in part orchestrating signal transduction of essential pathways that frequently are dysregulated in cancer, such as PI3K/Akt signaling and the Wnt/β-catenin pathway. CD133 expression correlates with enhanced cell self-renewal, migration, invasion, and survival under stress conditions in cancer. Aside from the intrinsic cell mechanisms that regulate CD133 expression in each cellular type, extrinsic factors from the surrounding niche can also impact CD33 levels. The enhanced CD133 expression in cells can confer adaptive advantages by amplifying the activation of a specific signaling pathway in a context-dependent manner. In this review, we do not only describe the CD133 physiological functions known so far, but importantly, we analyze how the microenvironment changes impact the regulation of CD133 functions emphasizing its value as a marker of cell adaptability beyond a cancer-stem cell marker.© 2023. The Author(s).