Significance of RB Loss in Unlocking Phenotypic Plasticity in Advanced Cancers.
Significance of RB Loss in Unlocking Phenotypic Plasticity in Advanced Cancers.
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DOI：
10.1158/1541-7786.mcr-23-0045
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发表时间：
2023-06-01
影响因子：
5.2
通讯作者：
Beltran, Himisha
中科院分区：
文献类型：
--
作者：
Venkadakrishnan, Varadha Balaji;Yamada, Yasutaka;Weng, Kenny;Idahor, Osasenaga;Beltran, Himisha
癌细胞可以在环境刺激或选择性治疗压力下经历可塑性，从而导致表型的变化。这种复杂的表型可塑性现象现在被认为是癌症的一个标志。谱系可塑性与对原始致癌驱动因素的依赖性丧失有关，并在一定程度上由潜在的基因组和表观遗传改变促进。了解癌症可塑性的分子驱动因素对于开发新的治疗策略至关重要。视网膜母细胞瘤基因RB1（编码RB）是第一个被发现的肿瘤抑制基因，在细胞周期调控中有很好的作用。RB还参与细胞周期以外的多种细胞功能，包括分化。在这里，我们描述了RB丢失在解锁癌症表型可塑性和驱动癌症类型的治疗抗性方面的新作用。我们强调了在癌症中的相似之处，即RB的非规范作用对正常发育和谱系规范至关重要，以及RB丢失的下游后果，包括表观遗传重编程和染色质重组，可导致谱系程序的变化。最后，我们讨论了针对rb丢失癌症进行谱系重编程的潜在治疗方法。
Cancer cells can undergo plasticity in response to environmental stimuli or under selective therapeutic pressures that result in changes in phenotype. This complex phenomenon of phenotypic plasticity is now recognized as a hallmark of cancer. Lineage plasticity is associated with loss of dependence on the original oncogenic driver and is facilitated, in part, by underlying genomic and epigenetic alterations. Understanding the molecular drivers of cancer plasticity is critical for the development of novel therapeutic strategies. The retinoblastoma gene RB1 (encoding RB) is the first tumor suppressor gene to be discovered and has a well-described role in cell-cycle regulation. RB is also involved in diverse cellular functions beyond cell cycle including differentiation. Here, we describe the emerging role of RB loss in unlocking cancer phenotypic plasticity and driving therapy resistance across cancer types. We highlight parallels in cancer with the non-canonical role of RB that is critical for normal development and lineage specification, and the downstream consequences of RB loss including epigenetic reprogramming and chromatin reorganization that can lead to changes in lineage program. Finally, we discuss potential therapeutic approaches geared towards RB-loss cancers undergoing lineage reprogramming.
影响因子：
8
作者：
Cheng, L.;Zhou, Z.;Flesken-Nikitin, A.;Toshkov, I. A.;Wang, W.;Camps, J.;Ried, T.;Nikitin, A. Y.
通讯作者：
Nikitin, A. Y.