Induction of Plac8 promotes pro-survival function of autophagy in cadmium-induced prostate carcinogenesis.
Induction of Plac8 promotes pro-survival function of autophagy in cadmium-induced prostate carcinogenesis.
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DOI：
10.1016/j.canlet.2017.08.023
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发表时间：
2017-11-01
期刊：
影响因子：
9.7
通讯作者：
Damodaran C
中科院分区：
文献类型：
--
作者：
Kolluru V;Pal D;Papu John AMS;Ankem MK;Freedman JH;Damodaran C
众所周知，长期接触镉是人类前列腺癌的风险因素。尽管有令人印象深刻的证据表明镉会导致人类致癌，但控制金属诱导细胞转化的具体潜在分子机制仍不清楚。急性镉暴露(长达72小时)可诱导正常前列腺上皮细胞(RWPE-1)的凋亡，而慢性暴露(>；1年)可将这些细胞转化为恶性表型(镉转化的前列腺上皮细胞；CTPE)。自噬调控基因PLAC8、LC3B和LAMP-1在CTPE细胞中的表达增加与镉诱导的转化有关。自噬/自溶酶体融合的调节因子PLAC8的表达增加，促进了自噬的促生存功能，并上调了PACT(SER473)和NF-κβ，使CTPE得以增殖。同样，抑制PLAC8也会抑制CTPE细胞的生长。此外，在RWPE-1细胞中过表达PLAC8可诱导对镉毒性的抗性。药物抑制剂和自噬诱导剂未能影响PLAC8的表达和CTPE细胞的活性，提示PLAC8在镉诱导的前列腺上皮细胞转化中具有独特的作用。这些结果支持了PLAC8在镉诱导的正常前列腺上皮细胞向癌变过程中所起的重要作用。
Chronic exposure to cadmium is known to be a risk factor for human prostate cancer. Despite over-whelming evidence of cadmium causing carcinogenicity in humans, the specific underlying molecular mechanisms that govern metal-induced cellular transformation remain unclear. Acute exposure (up to 72 hr) to cadmium induces apoptosis in normal prostate epithelial cells (RWPE-1), while chronic exposure (>1 year) transforms these cells to a malignant phenotype (cadmium-transformed prostate epithelial cells; CTPE). Increased expression of autophagy-regulated genes; Plac8, LC3B and Lamp-1; in CTPE cells was associated with cadmium-induced transformation. Increased expression of Plac8, a regulator of autophagosome/autolysosome fusion, facilitates the pro-survival function of autophagy and upregulation of pAKT(ser473) and NF-κβ, to allow CTPE to proliferate. Likewise, inhibition of Plac8 suppresses CTPE cell growth. Additionally, overexpression of Plac8 in RWPE-1 cells induces resistance to cadmium toxicity. Pharmacological inhibitors and an inducer of autophagy failed to affect Plac8 expression and CTPE cell viability, suggesting a unique role for Plac8 in cadmium-induced prostate epithelial cell transformation. These results support a role for Plac8 as an essential component in the cadmium-induced transformation of normal prostate epithelial cells to a cancerous state.
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影响因子：
37.3
作者：
Golovine, Konstantin;Makhov, Peter;Kolenko, Vladimir M.
通讯作者：
Kolenko, Vladimir M.
影响因子：
11.2
作者：
Kaistha, Brajesh P.;Lorenz, Holger;Buchholz, Malte
通讯作者：
Buchholz, Malte
影响因子：
3.3
作者：
Jung, Chang Hwa;Jun, Chang Bong;Kim, Do-Hyung
通讯作者：
Kim, Do-Hyung
影响因子：
13.3
作者：
Pi H;Xu S;Reiter RJ;Guo P;Zhang L;Li Y;Li M;Cao Z;Tian L;Xie J;Zhang R;He M;Lu Y;Liu C;Duan W;Yu Z;Zhou Z
通讯作者：
Zhou Z
DOI：
10.1126/science.1236566
发表时间：
2013-07-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kang SA;Pacold ME;Cervantes CL;Lim D;Lou HJ;Ottina K;Gray NS;Turk BE;Yaffe MB;Sabatini DM
通讯作者：
Sabatini DM