TSC22D2 interacts with PKM2 and inhibits cell growth in colorectal cancer
TSC22D2 interacts with PKM2 and inhibits cell growth in colorectal cancer
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TSC22D2 与 PKM2 相互作用并抑制结直肠癌细胞生长
DOI：
10.3892/ijo.2016.3599
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发表时间：
2016-09-01
影响因子：
5.2
通讯作者：
Xiong, Wei
中科院分区：
文献类型：
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作者：
Liang, Fang;Li, Qiao;Xiong, Wei
我们之前在一个罕见的多癌家族中鉴定出TSC22D2（转化生长因子刺激克隆22结构域家族成员2）是一种新的癌症相关基因。然而，其在肿瘤发生发展中的作用仍完全未知。在本研究中，我们发现TSC22D2在结直肠癌（CRC）中显著下调，且TSC22D2过表达可抑制细胞生长。通过免疫共沉淀（co - IP）实验结合质谱分析来鉴定与TSC22D2相互作用的蛋白质，我们证实TSC22D2与丙酮酸激酶M2亚型（PKM2）相互作用。免疫沉淀和免疫荧光实验结果进一步证实了这些发现。此外，TSC22D2过表达降低了细胞核中PKM2的水平，并抑制了细胞周期蛋白D1的表达。总体而言，我们的研究揭示了TSC22D2的生长抑制功能，该功能至少部分依赖于TSC22D2 - PKM2 - 细胞周期蛋白D1调控轴。此外，我们的数据为未来评估TSC22D2作用的研究提供了重要线索。
We previously identified TSC22D2 (transforming growth factor -stimulated clone 22 domain family, member 2) as a novel cancer-associated gene in a rare multi-cancer family. However, its role in tumor development remains completely unknown. In this study, we found that TSC22D2 was significantly downregulated in colorectal cancer (CRC) and that TSC22D2 overexpression inhibited cell growth. Using a co-immunoprecipitation (co-IP) assay combined with mass spectrometry analysis to identify TSC22D2-interacting proteins, we demonstrated that TSC22D2 interacts with pyruvate kinase isoform M2 (PKM2). These findings were confirmed by the results of immunoprecipitation and immunofluorescence assays. Moreover, overexpression of TSC22D2 reduced the level of nuclear PKM2 and suppressed cyclin D1 expression. Collectively, our study reveals a growth suppressor function of TSC22D2 that is at least partially dependent on the TSC22D2-PKM2-cyclinD1 regulatory axis. In addition, our data provide important clues that might contribute to future studies evaluating the role of TSC22D2.