Zhao Wei, Hao Lei, Jia Lizhou, Wang Jinsong, Wang Bin, Huang Yanqiang, Zhao Youcai
Research Center for The Prevention and Treatment of Drug Resistant Microbial Infecting, Youjiang Medical University for Nationalities Baise 533000, China.
Department of Pathology, Nanjing First Hospital, Nanjing Medical University Nanjing 210006, China.
Am J Cancer Res. 2021 Jun 15;11(6):3085-3097. eCollection 2021.
The morbidity and mortality of colorectal cancer (CRC) ranks fourth worldwide, moreover, the tumor microenvironment (TME) of CRC is quite complex, and is one of the necessary factors affecting promotion of tumor metastasis. PTPN2 is a tumor suppressor which plays an important role in cancer-related downstream molecular pathway. FSP-1 is highly-expressed in multiple types of tumor tissues and is a biomarker of stromal fibroblasts. To examine the function of PTPN2 in the metastasis of CRC, the study evaluated the co-expression level of PTPN2 and FSP-1 in CRC tissues by double staining, and demonstrated the relationship with clinical information about each patient. The roles of PTPN2 and FSP-1 were detected by proliferation and transwell assay through knockdown of expression level of PTPN2. Lower PTPN2 with higher FSP-1 expression was correlated with poor survival outcomes in CRC. TAFs contribute to the migration function of PTPN2 in CRC through inducing changes in the level of TGF-β1. Western blot and qRT-PCR assays were used to detect the mechanism of PTPN2 regulation of migration with TAFs in the JAK/STAT signaling pathway, moreover, TAFs contributed the function of PTPN2 in colorectal carcinogenesis . In summary, the study shed light on the effect of TAFs contributes the function of PTPN2 in colorectal carcinogenesis through activating JAK/STAT signaling pathway. In addition, double-staining assay could give us a unique perspective from which to study TME in CRC.
结直肠癌（CRC）的发病率和死亡率在全球排名第四，此外，CRC的肿瘤微环境（TME）非常复杂，是影响肿瘤转移促进的必要因素之一。PTPN2是一种肿瘤抑制因子，在癌症相关的下游分子通路中起重要作用。FSP-1在多种肿瘤组织中高表达，是基质成纤维细胞的生物标志物。为了研究PTPN2在CRC转移中的作用，该研究通过双重染色评估了CRC组织中PTPN2和FSP-1的共表达水平，并证明了其与每位患者临床信息的关系。通过敲低PTPN2的表达水平，采用增殖和Transwell实验检测PTPN2和FSP-1的作用。CRC中PTPN2表达较低而FSP-1表达较高与较差的生存结果相关。TAFs通过诱导TGF-β1水平的变化促进PTPN2在CRC中的迁移功能。采用蛋白质免疫印迹法（Western blot）和实时定量聚合酶链反应（qRT-PCR）实验检测PTPN2在JAK/STAT信号通路中与TAFs共同调控迁移的机制，此外，TAFs在结直肠癌发生过程中发挥了PTPN2的功能。总之，该研究揭示了TAFs通过激活JAK/STAT信号通路在结直肠癌发生过程中发挥PTPN2功能的作用。此外，双重染色实验可以为我们研究CRC中的TME提供一个独特的视角。
