SIRT1 promotes proliferation and inhibits the senescence-like phenotype in human melanoma cells.
SIRT1 promotes proliferation and inhibits the senescence-like phenotype in human melanoma cells.
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DOI：
10.18632/oncotarget.1791
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发表时间：
2014-04-30
期刊：
影响因子：
--
通讯作者：
Bertolotto C
中科院分区：
文献类型：
--
作者：
Ohanna M;Bonet C;Bille K;Allegra M;Davidson I;Bahadoran P;Lacour JP;Ballotti R;Bertolotto C
SIRT 1作为肿瘤抑制因子和致癌因子两者起作用，这取决于细胞环境。SIRT 1是否在黑色素瘤生物学中发挥作用仍然很难阐明。在这里，我们证明SIRT 1是黑色素瘤细胞增殖的关键调节因子。通过遗传或药理学方法抑制SIRT 1诱导细胞周期停滞和衰老样表型。功能获得和丧失实验表明，M-MITF调节SIRT 1表达，从而揭示了黑素细胞特异性控制SIRT 1。SIRT 1过表达缓解了MITF抑制引起的衰老样表型和增殖停滞，表明SIRT 1是MITF诱导的黑色素瘤细胞增殖的效应子。有趣的是，与其敏感的对应物相比，PLX 4032抗性BRAFV 600 E突变的黑素瘤细胞中的SIRT 1水平和活性增强。SIRT 1抑制降低黑色素瘤细胞生长并挽救PLX 4032抗性BRAFV 600 E突变黑色素瘤细胞对PLX 4032的敏感性。总之，我们提供了第一个证据表明SIRT 1的抑制值得考虑作为一种抗黑色素瘤治疗选择。
SIRT1 operates as both a tumor suppressor and oncogenic factor depending on the cell context. Whether SIRT1 plays a role in melanoma biology remained poorly elucidated. Here, we demonstrate that SIRT1 is a critical regulator of melanoma cell proliferation. SIRT1 suppression by genetic or pharmacological approaches induces cell cycle arrest and a senescence-like phenotype. Gain and loss of function experiments show that M-MITF regulates SIRT1 expression, thereby revealing a melanocyte-specific control of SIRT1. SIRT1 over-expression relieves the senescence-like phenotype and the proliferation arrest caused by MITF suppression, demonstrating that SIRT1 is an effector of MITF-induced proliferation in melanoma cells. Interestingly, SIRT1 level and activity are enhanced in the PLX4032-resistant BRAFV600E-mutated melanoma cells compared with their sensitive counterpart. SIRT1 inhibition decreases melanoma cell growth and rescues the sensibility to PLX4032 of PLX4032-resistant BRAFV600E-mutated melanoma cells. In conclusion, we provide the first evidence that inhibition of SIRT1 warrants consideration as an anti-melanoma therapeutic option.
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影响因子：
64.8
作者：
Bertolotto, Corine;Lesueur, Fabienne;Bressac-de Paillerets, Brigitte
通讯作者：
Bressac-de Paillerets, Brigitte
影响因子：
10.5
作者：
Larribere, L;Hilmi, C;Bertolotto, C
通讯作者：
Bertolotto, C
影响因子：
5.7
作者：
Cerezo, Michael;Tichet, Melanie;Rocchi, Stephane
通讯作者：
Rocchi, Stephane
影响因子：
11.2
作者：
Giuliano, Sandy;Cheli, Yann;Bertolotto, Corine
通讯作者：
Bertolotto, Corine
影响因子：
3.7
作者：
Kabbarah O;Nogueira C;Feng B;Nazarian RM;Bosenberg M;Wu M;Scott KL;Kwong LN;Xiao Y;Cordon-Cardo C;Granter SR;Ramaswamy S;Golub T;Duncan LM;Wagner SN;Brennan C;Chin L
通讯作者：
Chin L