《癌细胞》：科学家发现癌症的共同点

资讯作者：Lunenfeld-Tanenbaum Research Institute

编辑翻译：奇奇

本文献于2021年7月发表在国际著名医学期刊《癌细胞》（Cancer Cell）。西奈卫生院的科学家们根据一种蛋白质将癌症分为两类，通过对该蛋白质的研究，他们有望找出癌症的弱点，开发出新的癌症治疗策略。

西奈卫生院的科学家们研究发现，所有的癌症都可分为两类，该发现能够为治疗最具侵袭性或无法治愈的癌症提供一种新的治疗策略。

本月发表在《癌细胞》上的一项新研究中，西奈卫生院分部LTRI研究所的科学家们根据是否存在一种被称为YAP的蛋白质，将癌症分为两类。

LTRI的高级科学家RodBremner说，他们已经确定所有癌症都存在YAP，不管是处于开启还是关闭状态，每种分类的癌症都表现出不同的药物敏感性或耐药性。YAP在恶性肿瘤的形成中起着重要作用，因为它是Hippo信号通路的重要调控和效应因子。

Bremner说：“在任何情况下，不管YAP是关闭还是开启，它都有相反的促进或者抗癌作用。因此，YAP开启的癌症需要YAP才能生存和生长，相反，当我们开启YAP时，YAP关闭的癌症就会停止生长。”

很多YAP关闭的癌症都是高度致死的。在他们的新研究中，Bremner和来自纽约布法罗罗斯威尔帕克综合癌症中心的其他研究人员表明，像前列腺癌和肺癌等一些癌症可以将YAP从开启状态跳转到关闭状态，从而抵抗治疗。

当实验室环境中的癌细胞在培养皿中生长时，癌细胞或者漂浮，或者粘住。研究团队发现，YAP是细胞浮力的主要调节器，所有漂浮细胞的YAP处于开启状态，而所有粘性细胞的YAP处于关闭状态。Bremner解释道，已知粘附行为的变化与药物耐性有关，所以他们的发现也说明了YAP处于这个开关的中心地位。

Joel Pearson是LTRI研究所Bremner实验室的博士后研究员和主要联合者。他表示，癌症的治疗方法可能会对患者的生存产生深远影响。

Pearson说：“我们发现的简单二元规则可能揭示了许多癌症的治疗策略，不管是YAP开启的癌症，还是YAP关闭的癌症。此外，癌症会出现跳跃状态以逃避治疗，所以调整YAP的开启或关闭状态可能是一种通用的治疗方法，以用来阻止癌症转变为耐药性类型。”

研究人员希望通过研究推断出这些类型癌症的共同弱点，以开发出新的治疗方法，并且改善患者的预后。

英文原文

New Research Finds Common Denominator Linking All Cancers

All cancers fall into just two categories, according to new research from scientists at Sinai Health, in findings that could provide a new strategy for treating the most aggressive and untreatable forms of the disease.

In new research out this month in Cancer Cell, scientists at the Lunenfeld-Tanenbaum Research Institute (LTRI), part of Sinai Health, divide all cancers into two groups, based on the presence or absence of a protein called the Yes-associated protein, or YAP.

Rod Bremner, senior scientist at the LTRI, said they have determined that all cancers are present with YAP either on or off, and each classification exhibits different drug sensitivities or resistance. YAP plays an important role in the formation of malignant tumours because it is an important regulator and effector of the Hippo signaling pathway.

“Not only is YAP either off or on, butit has opposite pro- or anti-cancer effects in either context,” Bremnersaid. “Thus, YAPon cancers need YAP to grow and survive. In contrast, YAPoff cancers stop growing when we switch on YAP.”

Many YAPoff cancers are highly lethal. In their new research, Bremner and fellow researchers from the Roswell Park Comprehensive Cancer Center in Buffalo, NY, show that some cancers like prostate and lung can jump from a YAPon state to a YAPoff state to resist therapeutics.

When cancer cells are grown in a dish in alab setting, they either float or stick down. The team of researchers found that YAP is the master regulator of a cell's buoyancy, where all the floating cells are YAPoff, and all the sticky cells are YAPon. Changes in adhesive behavior are well known to be associated with drug resistance, so their findings implicates YAP at the hub of this switch, explained Bremner.

Joel Pearson, co-lead author and a post-doctoral fellow in the Bremner Lab at the LTRI, said therapies that tackle these cancers could have a profound effect on patient survival.

“The simple binary rule we uncovered may expose strategies to treat many cancer types that fall into either the YAPoff or YAPon superclasses,” Pearson said. “Moreover, since cancers jump states to evade therapy, having ways to treat either the YAPoff and YAPon state could become a general approach to stop this cancer from switching types to resist drug treatments.”

The researchers hope by deducing common vulnerabilities of these types of cancer, it may be possible to develop new therapeutic approaches and improve patient outcomes.

参考文献 

Joel D.Pearsone et al, Binary pan-cancer classes with distinct vulnerabilities defined by pro- or anti-cancer YAP/TEAD activity, Cancer Cell (2021).

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