Functions and regulation of MUC13 mucin in colon cancer cells.
Functions and regulation of MUC13 mucin in colon cancer cells.
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DOI：
10.1007/s00535-013-0885-z
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发表时间：
2014-10
影响因子：
6.3
通讯作者：
Chauhan, Subhash C.
中科院分区：
文献类型：
--
作者：
Gupta, Brij K.;Maher, Diane M.;Ebeling, Mara C.;Stephenson, Phillip D.;Puumala, Susan E.;Koch, Michael R.;Aburatani, Hiroyuki;Jaggi, Meena;Chauhan, Subhash C.
MUC 13在结肠癌组织中过度表达并异常定位;然而，MUC 13表达的具体功能和调控尚不清楚。分析具有过表达或抑制的MUC 13水平的稳定细胞系以确定细胞生长、集落形成、细胞迁移和细胞侵袭测定。通过染色质免疫沉淀（ChIP）和白细胞介素6（IL 6）治疗的分析阐明了MUC 13调控的分子机制。通过免疫组织化学（IHC）分析结肠癌组织中结肠癌细胞中MUC 13和P-STAT 5的蛋白水平。MUC 13的过表达增加了细胞生长、集落形成、细胞迁移和侵袭。一致地，MUC 13沉默降低了这些致瘤特征。MUC 13的过表达还调节多种癌症相关蛋白，包括端粒酶逆转录酶（TERT）、音刺猬（SHH）、B细胞淋巴瘤鼠样位点1（BMI-1）和加塔样转录因子1（GATA 1）。此外，MUC 13过表达细胞显示HER 2和P-ERK表达增加。ChIP分析揭示了STAT 5与预测的MUC 13启动子的结合。IL 6处理结肠癌细胞通过激活JAK 2/STAT 5信号通路增加MUC 13的表达。通过化学抑制剂抑制JAK 2和STAT 5信号传导消除了IL 6诱导的MUC 13表达。IHC分析显示，与邻近的正常组织相比，结肠癌中P-STAT 5和MUC 13的表达增加。该研究的结果首次表明MUC 13在结肠癌进展中的功能作用，并提供了关于通过JAK 2/STAT 5调节MUC 13表达的信息，这可能揭示结肠癌治疗的有希望的治疗方法。
MUC13 is over-expressed and aberrantly localized in colon cancer tissue; however, the specific functions and regulation of MUC13 expression are unknown. Stable cell lines with either over-expressed or suppressed MUC13 levels were analyzed to determine cell growth, colony formation, cell migration, and cell invasion assays. The molecular mechanisms involved in MUC13 regulation were elucidated via chromatin immunoprecipitation (ChIP) and analysis of interleukin 6 (IL6) treatments. Colon cancer tissues were analyzed by immunohistochemistry (IHC) for the protein levels of MUC13 and P-STAT5 in colon cancer cells. Over-expression of MUC13 increased cell growth, colony formation, cell migration, and invasion. In concordance, MUC13 silencing decreased these tumorigenic features. Over-expression of MUC13 also modulated various cancer-associated proteins, including telomerase reverse transcriptase (TERT), sonic hedgehog (SHH), B cell lymphoma murine like site 1 (BMI-1), and GATA like transcription factor 1 (GATA1). Additionally, MUC13 over-expressing cells showed increased HER2 and P-ERK expression. ChIP analysis revealed binding of STAT5 to the predicted MUC13 promoter. IL6 treatment of colon cancer cells increased the expression of MUC13 via activation of JAK2/STAT5 signaling pathway. Suppression of JAK2 and STAT5 signaling by chemical inhibitors abolished IL6 induced MUC13 expression. IHC analysis showed increased expression of both P-STAT5 and MUC13 in colon cancer as compared to adjacent normal tissue The results of this study, for the first time, suggest functional roles of MUC13 in colon cancer progression and provide information regarding the regulation of MUC13 expression via JAK2/STAT5 which may reveal promising therapeutic approaches for colon cancer treatment.
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影响因子：
5.7
作者：
Chauhan SC;Ebeling MC;Maher DM;Koch MD;Watanabe A;Aburatani H;Lio Y;Jaggi M
通讯作者：
Jaggi M
影响因子：
2.2
作者：
HAYASHI, Y;WIDJONO, YW;ITOH, H
通讯作者：
ITOH, H
影响因子：
3.1
作者：
Camporeale, Annalisa;Poli, Valeria
通讯作者：
Poli, Valeria
影响因子：
2.6
作者：
Komoda, H;Tanaka, Y;Takao, T
通讯作者：
Takao, T
影响因子：
3.2
作者：
Gupta, Brij K.;Maher, Diane M.;Chauhan, Subhash C.
通讯作者：
Chauhan, Subhash C.