Receptor-interacting protein (RIP) and Sirtuin-3 (SIRT3) are on opposite sides of anoikis and tumorigenesis.
Receptor-interacting protein (RIP) and Sirtuin-3 (SIRT3) are on opposite sides of anoikis and tumorigenesis.
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DOI：
10.1002/cncr.27655
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发表时间：
2012-12-01
期刊：
影响因子：
6.2
通讯作者：
Kapila, Yvonne L.
中科院分区：
文献类型：
--
作者：
Kamarajan, Pachiyappan;Alhazzazi, Turki Y.;Danciu, Theodora;D'silva, Nisha J.;Verdin, Eric;Kapila, Yvonne L.
关键词：
调节失巢凋亡和生存信号通路之间的串扰对于调节组织过程和减轻癌症等疾病至关重要。之前，我们发现失巢凋亡激活由受体相互作用蛋白（RIP）调节的CD95/Fas介导的信号通路，RIP是一种在Fas介导的细胞死亡和整合素/FAK介导的生存通路之间穿梭的激酶。由于 Sirtuin-3 (SIRT3) 是一种 NAD 依赖性脱乙酰酶，已知可调节细胞存活、代谢和肿瘤发生，因此我们假设 SIRT3 可能与癌细胞系统中的 Fas/RIP/整合素/FAK 生存-死亡途径发生串扰。使用免疫组织化学染色、免疫印迹、人体组织微阵列以及体外和体内过表达和抑制方法，我们检查了 RIP 和 SIRT3 在口腔鳞状细胞癌 (OSCC) 失巢凋亡抵抗和肿瘤发生中的作用。 RIP 和 SIRT3 在 OSCC 细胞和组织中具有相反的表达谱。 RIP 的稳定抑制会增强 SIRT3 水平，而 SIRT3 的稳定抑制不会影响 OSCC 细胞中的 RIP 水平。当 OSCC 细胞变得抗失巢凋亡时，它们在悬浮条件下形成多细胞聚集体或 oraspheres，并且它们的 SIRT3 表达随着 RIP 表达的减少而增加。此外，与贴壁 OSCC 细胞不同，具有较高 SIRT3 和低 RIP 表达的抗失巢凋亡 OSCC 细胞会导致小鼠肿瘤负荷和发病率增加。此外，稳定抑制 SIRT3 可抑制失巢凋亡抵抗并降低肿瘤发生率。 RIP 可能是 SIRT3 在失巢凋亡抗性中的上游负调节因子，由较高 SIRT3 和低 RIP 表达定义的抗失巢凋亡 orasphere 表型有助于 OSCC 发展中更具侵袭性的表型。
Regulating crosstalk between anoikis and survival signaling pathways is crucial to regulating tissue processes and mitigating diseases like cancer. Previously, we showed that anoikis activates a CD95/Fas-mediated signaling pathway regulated by receptor-interacting protein (RIP), a kinase that shuttles between Fas-mediated cell death and integrin/FAK-mediated survival pathways. Since sirtuin-3 (SIRT3), an NAD-dependent deacetylase, is known to regulate cell survival, metabolism, and tumorigenesis, we hypothesized that SIRT3 might engage in crosstalk with Fas/RIP/integrin/FAK survival-death pathways in cancer cell systems. Using immunohistochemical staining, immunoblotting, human tissue microarrays, and overexpression and suppression approaches in vitro and in vivo we examined the roles of RIP and SIRT3 in oral squamous cell carcinoma (OSCC) anoikis resistance and tumorigenesis. RIP and SIRT3 have an opposite expression profile in OSCC cells and tissues. Stable suppression of RIP enhances SIRT3 levels, whereas, stable suppression of SIRT3 does not impact RIP levels in OSCC cells. As OSCC cells become anoikis-resistant they form multicellular aggregates or oraspheres in suspension conditions, and their expression of SIRT3 increases as their RIP expression decreases. Also, anoikis-resistant OSCC cells with higher SIRT3 and low RIP expression induce an increased tumor burden and incidence in mice unlike their adherent OSCC cell counterparts. Furthermore, stable suppression of SIRT3 inhibits anoikis resistance and reduces tumor incidence. RIP is a likely upstream negative regulator of SIRT3 in anoikis resistance, and an anoikis-resistant orasphere phenotype defined by higher SIRT3 and low RIP expression contributes to a more aggressive phenotype in OSCC development.
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影响因子：
3.7
作者：
Li S;Banck M;Mujtaba S;Zhou MM;Sugrue MM;Walsh MJ
通讯作者：
Walsh MJ
DOI：
10.1186/bcr2106
发表时间：
2008
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Grimshaw MJ;Cooper L;Papazisis K;Coleman JA;Bohnenkamp HR;Chiapero-Stanke L;Taylor-Papadimitriou J;Burchell JM
通讯作者：
Burchell JM
影响因子：
8
作者：
Jin, Lei;Galonek, Heidi;Westphal, Christoph H.
通讯作者：
Westphal, Christoph H.
影响因子：
3.5
作者：
Kasof, GM;Prosser, JC;Gomes, BC
通讯作者：
Gomes, BC
影响因子：
4
作者：
Marfe, Gabriella;Tafani, Marco;Russo, Matteo Antonio
通讯作者：
Russo, Matteo Antonio