Background

Carcinogenesis is governed by a series of genetic alterations and epigenetic changes that lead to aberrant patterns in neoplastic cells. Sirtuin-1(SIRT1), an NAD⁺-dependent protein deacetylase, is capable of deacetylating histones and non-histone substrates that regulate various physiological activities during tumorigenesis. Recent studies have identified the role of SIRT1 in different stages of cancer, including genome instability, tumor initiation, proliferation, metabolism, and therapeutic response. However, the action of SIRT1 has been reported to be both oncogenic and tumor suppressive during carcinogenesis. Consequently, the biological functions of SIRT1 in cancer remain controversial.

Scope of review

We highlight the most recent findings on SIRT1 in different stages of tumorigenesis, and update the current status of SIRT1 small molecule modulators in clinical application of cancer treatment.

Major conclusion

By targeting both tumor suppressors and oncogenic proteins, SIRT1 has a bifunctional role at different stages of tumorigenesis. The impact of SIRT1 on tumorigenesis is also distinct at different stages and is dependent on its dosages. SIRT1 suppresses tumor initiation through its functions in promoting DNA repair, increasing genome stability, and inhibiting inflammation at the pre-cancer stage. However, SIRT1 enhances tumor proliferation, survival, and drug resistance through its roles in anti-apoptosis, pro-tumor metabolism, and anti-inflammation (inhibition of anti-tumor immunity) at the stages of tumor progression, metastasis, and relapse. Consequently, both SIRT1 inhibitors and activators have been explored for cancer treatment.

General significance

Better understanding the dose- and stage-dependent roles of SIRT1 in each cancer type can provide new avenues of exploration for therapy development.

中文翻译：

---

SIRT1 在致瘤性方面的热门话题

背景

癌变受一系列遗传改变和表观遗传改变控制，这些改变和表观遗传改变导致肿瘤细胞的异常模式。Sirtuin-1(SIRT1) 是一种 NAD ⁺依赖性蛋白质脱乙酰酶，能够使组蛋白和非组蛋白底物去乙酰化，从而调节肿瘤发生过程中的各种生理活动。最近的研究已经确定了 SIRT1 在癌症不同阶段的作用，包括基因组不稳定性、肿瘤起始、增殖、代谢和治疗反应。然而，据报道 SIRT1 的作用在致癌过程中具有致癌性和肿瘤抑制性。因此，SIRT1 在癌症中的生物学功能仍存在争议。

审查范围

我们重点介绍了 SIRT1 在肿瘤发生不同阶段的最新发现，并更新了 SIRT1 小分子调节剂在癌症治疗临床应用中的现状。

主要结论

通过靶向肿瘤抑制因子和致癌蛋白，SIRT1 在肿瘤发生的不同阶段具有双重功能。SIRT1 对肿瘤发生的影响在不同阶段也不同，并且取决于其剂量。SIRT1 通过其促进 DNA 修复、增加基因组稳定性和抑制癌前阶段炎症的功能来抑制肿瘤的发生。然而，SIRT1 通过其在肿瘤进展、转移和复发阶段的抗凋亡、促肿瘤代谢和抗炎（抑制抗肿瘤免疫）的作用来增强肿瘤的增殖、存活和耐药性。因此，已经探索了 SIRT1 抑制剂和激活剂用于癌症治疗。

一般意义

更好地了解 SIRT1 在每种癌症类型中的剂量和阶段依赖性作用可以为治疗开发提供新的探索途径。