Manganese superoxide dismutase (Sod2) and redox-control of signaling events that drive metastasis.
Manganese superoxide dismutase (Sod2) and redox-control of signaling events that drive metastasis.
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DOI：
10.2174/187152011795255911
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发表时间：
2011-02
影响因子：
2.8
通讯作者：
Melendez JA
中科院分区：
文献类型：
--
作者：
Hempel N;Carrico PM;Melendez JA
锰超氧化物歧化酶（Sod2）是在肿瘤发生过程中发挥双重作用的关键酶。早期的研究主要是基于Sod2在许多肿瘤类型中的低水平表达来确定其肿瘤抑制功能。现在普遍认为，Sod2表达的缺失可能是肿瘤进展的早期事件，允许由自由基产生的稳态增加引起的致瘤表型的进一步传播。自由基负荷的增加也与线粒体功能缺陷和转移性疾病进展有关。最初认为，Sod2的丢失可能会促进转移性疾病的进展，但实际上，流行病学和实验证据表明，在许多肿瘤类型中，当它们从早期非侵袭性疾病发展到晚期转移性疾病时，Sod2水平会升高。在许多情况下，Sod2过表达增强了转移表型，而这种转移表型被有效的H2O2清除所逆转。本综述评估了许多与影响转移表型的Sod2升高相关的后遗症。利用Sod2调节细胞氧化还原环境的能力已经允许识别驱动恶性肿瘤的氧化还原反应信号事件，如侵袭、迁移和延长肿瘤细胞存活。对这些氧化还原驱动事件的进一步研究将有助于制定有针对性的治疗策略，以有效地限制恶性进展所必需的氧化还原信号。
Manganese superoxide dismutase (Sod2) has emerged as a key enzyme with a dual role in tumorigenic progression. Early studies were primarily directed at defining the tumor suppressive function of Sod2 based on its low level expression in many tumor types. It is now commonly held that loss of Sod2 expression is likely an early event in tumor progression allowing for further propagation of the tumorigenic phenotype resulting from steady state increases in free radical production. Increases in free radical load have also been linked to defects in mitochondrial function and metastatic disease progression. It was initially believed that Sod2 loss may propagate metastatic disease progression, in reality both epidemiologic and experimental evidence indicate that Sod2 levels increase in many tumor types as they progress from early stage non-invasive disease to late stage metastatic disease. Sod2 overexpression in many instances enhances the metastatic phenotype that is reversed by efficient H2O2 scavenging. This review evaluates the many sequelae associated with increases in Sod2 that impinge on the metastatic phenotype. The ability to use Sod2 to modulate the cellular redox-environment has allowed for the identification of redox-responsive signaling events that drive malignancy, such as invasion, migration and prolonged tumor cell survival. Further studies of these redox-driven events will help in the development of targeted therapeutic strategies to efficiently restrict redox-signaling essential for malignant progression.
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影响因子：
6.6
作者：
DINNEY, CPN;FISHBECK, R;KILLION, JJ
通讯作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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