Adipocyte-driven unfolded protein response is a shared transcriptomic signature of metastatic prostate carcinoma cells.
Adipocyte-driven unfolded protein response is a shared transcriptomic signature of metastatic prostate carcinoma cells.
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DOI：
10.1016/j.bbamcr.2021.119101
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Podgorski I
中科院分区：
文献类型：
--
作者：
Herroon MK;Mecca S;Haimbaugh A;Garmo LC;Rajagurubandara E;Todi SV;Baker TR;Podgorski I
在骨骼转移领域，一个关键的未知问题是癌细胞如何找到在恶劣条件下生长的方法，前列腺癌细胞对富含脂肪细胞的骨髓进行转移性定植就是例证。为了开始了解使肿瘤细胞能够在困难的微环境(如骨骼)中生存和发展的分子过程，我们在没有或存在骨髓脂肪细胞的情况下，对两种不同的前列腺癌细胞系的转录组进行了无偏见的检查。我们的RNAseq分析以及随后的定量PCR和基于蛋白质的分析表明，内质网(ER)应激和未折叠蛋白反应(UPR)基因的上调是两个不同来源的转移性前列腺癌细胞株的共同特征。途径分析和药理学检查强调ER伴侣BIP是这一转录信号的上游协调者。更多基于患者的数据支持我们的总体结论，即ER应激和UPR诱导是转移性肿瘤细胞对其微环境的反应和适应的共同重要因素。我们的研究为进一步的机制研究铺平了道路，并为转移性疾病的有效治疗干预提供了新的线索。
A critical unknown in the field of skeletal metastases is how cancer cells find a way to thrive under harsh conditions, as exemplified by metastatic colonization of adipocyte-rich bone marrow by prostate carcinoma cells. To begin understanding molecular processes that enable tumor cells to survive and progress in difficult microenvironments such as bone, we performed unbiased examination of the transcriptome of two different prostate cancer cell lines in the absence or presence of bone marrow adipocytes. Our RNAseq analyses and subsequent quantitative PCR and protein-based assays reveal that upregulation of Endoplasmic Reticulum (ER) stress and Unfolded Protein Response (UPR) genes is a shared signature between two metastatic prostate carcinoma cell lines of different origin. Pathway analyses and pharmacological examinations highlight the ER chaperone BIP as an upstream coordinator of this transcriptomic signature. Additional patient-based data support our overall conclusion that ER stress and UPR induction are shared, important factors in the response and adaptation of metastatic tumor cells to their micro-environment. Our studies pave the way for additional mechanistic investigations and offer new clues towards effective therapeutic interventions in metastatic disease.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
4.3
作者：
Diedrich JD;Herroon MK;Rajagurubandara E;Podgorski I
通讯作者：
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作者：
Balaban, Seher;Nassar, Zeyad D.;Hoy, Andrew J.
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影响因子：
5.3
作者：
Blais, JD;Filipenko, V;Bell, JC
通讯作者：
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影响因子：
--
作者：
Diedrich JD;Rajagurubandara E;Herroon MK;Mahapatra G;Hüttemann M;Podgorski I
通讯作者：
Podgorski I