GOLPH3 Promotes Cancer Growth by Interacting With STIP1 and Regulating Telomerase Activity in Pancreatic Ductal Adenocarcinoma.
GOLPH3 Promotes Cancer Growth by Interacting With STIP1 and Regulating Telomerase Activity in Pancreatic Ductal Adenocarcinoma.
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GOLPH3 通过与 STIP1 相互作用并调节胰管腺癌中的端粒酶活性促进癌症生长
DOI：
10.3389/fonc.2020.575358
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发表时间：
2020
影响因子：
4.7
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Wang K;Jiang S;Huang A;Gao Y;Peng B;Li Z;Ma W;Songyang Z;Zhang S;He M;Li W
高尔基体磷蛋白3（GOLPH 3）的过表达预示着预后不良，是胰腺导管腺癌（PDAC）的潜在治疗靶点。然而，其在PDAC进展中的作用和潜在的分子机制仍不清楚。在本研究中，使用高通量双分子荧光互补（BiFC）分析，我们确定了应激诱导蛋白-1（STIP 1）与GOLPH 3相互作用，并使用共定位和免疫共沉淀证实了这种相互作用。采用免疫组化（IHC）和实时定量逆转录PCR检测PDAC组织和癌旁胰腺组织中GOLPH 3和STIP 1的水平。应用实时定量端粒重复序列扩增（Q-TRAP）技术检测PDAC细胞端粒酶相对活性，并检测靶向GOLPH 3或STIP 1的小干扰RNA转染PDAC细胞后细胞增殖情况。BALB/c裸鼠用于评估用GOLPH 3短发夹RNA稳定转染的BXPC 3细胞的肿瘤生长抑制。总之，发现GOLPH 3与STIP 1相互作用，并且这两种蛋白在PDAC组织和细胞系中过表达并共定位。此外，在PANC 1和BXPC 3细胞中使用shRNA抑制GOLPH 3表达在体外和体内均抑制肿瘤细胞增殖。GOLPH 3与STIP 1相互作用，通过c-Myc激活端粒酶逆转录酶（hTERT）和端粒酶活性，上调细胞周期相关信号蛋白cyclin D1，促进肿瘤细胞生长，提示阻断STIP 1与GOLPH 3之间的相互作用可能是治疗PDAC的新策略。
Overexpression of Golgi phosphoprotein 3 (GOLPH3) predicts poor prognosis and is a potential therapeutic target in pancreatic ductal adenocarcinoma (PDAC). However, its role and underlying molecular mechanisms in the progression of PDAC remain unknown. In the present study, using high-throughput bimolecular fluorescence complementation (BiFC) analysis, we identified that stress-inducible protein-1 (STIP1) interacts with GOLPH3 and confirmed the interaction using co-localization and co-immunoprecipitation. The levels of GOLPH3 and STIP1 in PDAC tissues and adjacent non-cancerous pancreatic tissues were determined using immunohistochemistry (IHC) and quantitative real-time reverse transcription PCR. Real-time Quantitative-telomere repeat amplification (Q-TRAP) was applied to detect relative telomerase activity, and cell proliferation was measured when small interfering RNAs targeting GOLPH3 or STIP1 were transfected into PDAC cell lines. BALB/c nude mice were used to assess tumor growth inhibition of BXPC3 cells stably transfected with GOLPH3 short hairpin RNA. In summary, GOLPH3 was found to interact with STIP1 and both proteins were overexpressed and co-localized in PDAC tissues and cell lines. Moreover, suppression of GOLPH3 expression using shRNAs in PANC1 and BXPC3 cells inhibited tumor cell proliferation both in vitro and in vivo. Mechanistically, GOLPH3 interacts with STIP1 to activate telomerase reverse transcriptase (hTERT) and telomerase activity by c-Myc, and then upregulates cell cycle-related signaling proteins, including cyclin D1, to promote tumor cell growth, suggesting that disrupting the interaction between STIP1 and GOLPH3 would be a promising new strategy to treat PDAC.
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影响因子：
64.8
作者：
Park, Jae-Il;Venteicher, Andrew S.;Hong, Ji Yeon;Choi, Jinkuk;Jun, Sohee;Shkreli, Marina;Chang, Woody;Meng, Zhaojing;Cheung, Peggie;Ji, Hong;McLaughlin, Margaret;Veenstra, Timothy D.;Nusse, Roel;McCrea, Pierre D.;Artandi, Steven E.
通讯作者：
Artandi, Steven E.
影响因子：
3.7
作者：
Kumari, Alpana;Srinivasan, Radhika;Wig, Jai Dev
通讯作者：
Wig, Jai Dev
高尔基体磷蛋白 3 (GOLPH3) 通过激活 NF-κB 通路促进肝细胞癌细胞侵袭性
影响因子：
7.3
作者：
Dai, Ting;Zhang, Dongsheng;Song, Libing
通讯作者：
Song, Libing
影响因子：
3.7
作者：
Kim, Sunghoon;Cho, HanByoul;Kim, Jae-Hoon
通讯作者：
Kim, Jae-Hoon
DOI：
10.1080/10799893.2020.1719152
发表时间：
2020-02-06
影响因子：
2.8
作者：
Pan, Lei;Duan, Yin;Lou, Lihua
通讯作者：
Lou, Lihua