Proteomics Suggests a Role for APC-Survivin in Response to Somatostatin Analog Treatment of Neuroendocrine Tumors

蛋白质组学表明 APC-Survivin 在神经内分泌肿瘤生长抑素类似物治疗中发挥重要作用

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作者:Omid Fotouhi, Hanna Kjellin, Catharina Larsson, Jamileh Hashemi, Jorge Barriuso, C Christofer Juhlin, Ming Lu, Anders Höög, Laura G Pastrián, Angela Lamarca, Victoria Heredia Soto, Jan Zedenius, Marta Mendiola, Janne Lehtiö, Magnus Kjellman

Conclusions

We report a proteome-wide analysis of changes in response to lanreotide in NET cell lines. This analysis suggests a connection between somatostatin analog, APC, and survivin levels. Survivin is a possible prognostic factor and a new potential therapeutic target in NETs.

Results

We quantified 6451 and 7801 proteins in HC45 and H727, respectively. After short time lanreotide treatment APC was increased and survivin reduced. Overexpression of APC in H727 cells decreased, and APC knock-down elevated the survivin level. The lanreotide regulation of APC-survivin could be suppressed by small interfering RNA against somatostatin receptor 2. Although lanreotide only gave slight inhibition of proliferation, targeting of survivin with the small molecule YM155 dramatically reduced proliferation. Moderate or high as compared with low or absent total survivin expression was associated with shorter progression-free survival, independent of tumor stage, grade, and localization. Conclusions: We report a proteome-wide analysis of changes in response to lanreotide in NET cell lines. This analysis suggests a connection between somatostatin analog, APC, and survivin levels. Survivin is a possible prognostic factor and a new potential therapeutic target in NETs.

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