Overexpression of a novel regulator of p120 catenin, NLBP, promotes lung adenocarcinoma proliferation
Overexpression of a novel regulator of p120 catenin, NLBP, promotes lung adenocarcinoma proliferation
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DOI：
10.4161/cc.25451
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发表时间：
2013-08-01
期刊：
影响因子：
4.3
通讯作者：
Kim, Hongtae
中科院分区：
文献类型：
--
作者：
Kim, Chang Hee;Nam, Hae-Seong;Kim, Hongtae
NLBP（新型lzap结合蛋白）最近被证明是一种能够抑制NFB信号通路的肿瘤抑制因子。NLBP也被认为是细胞侵袭的负调节因子，它的表达在几种侵袭活性很小的癌细胞系中降低。尽管这些现象提示NLBP可能是一种潜在的肿瘤抑制因子，但其在人类肺癌中的抑瘤作用尚未得到很好的证实。与我们的预期相反，NLBP在肺腺癌组织的早期高表达，NLBP的过表达促进了H1299肺腺癌细胞的增殖。我们还发现p120 catenin （p120ctn）是NLBP的一个新的结合伙伴，NLBP结合p120ctn的调控区域，p120ctn分别与NLBP的n端区域结合。这种结合导致p120ctn稳定，通过抑制其泛素化抑制p120ctn的蛋白酶体降解。此外，我们还发现NLBP和p120ctn在人肺癌中的过表达与腺癌的发生密切相关，而非鳞状细胞癌。综上所述，我们的研究结果表明NLBP在人肺腺癌中高度过表达，NLBP的过表达通过与p120ctn相互作用促进肺腺癌细胞增殖，提示NLBP可能在肺腺癌的早期癌变过程中起到致癌基因的作用。
NLBP (novel LZAP-binding protein) was recently shown to function as a tumor suppressor capable of inhibiting the NFB signaling pathway. NLBP is also known as a negative regulator of cell invasion, and its expression is reduced in several cancer cell lines that have little invasive activity. Although these phenomena suggest that NLBP may be a potential tumor suppressor, its role as a tumor suppressor in human lung cancer is not well established. In contrast to our expectation, NLBP was highly expressed in the early stage of lung adenocarcinoma tissues, and overexpression of NLBP promoted proliferation of H1299 lung adenocarcinoma cells. We also found that p120 catenin (p120ctn) was a novel binding partner of NLBP, and that NLBP binds to the regulatory domain of p120ctn, and p120ctn associates with N-terminal region of NLBP, respectively. This binding leads to p120ctn stability to inhibit proteasomal degradation of p120ctn by inhibiting its ubiqutination. In addition, we also found that overexpression of NLBP and p120ctn in human lung cancer are closely related with adenocarcinoma compared with squamous cell carcinoma. Taken together, our findings reveal that NLBP is highly overexpressed in human lung adenocarcinoma, and that overexpression of NLBP promotes the cell proliferation of lung adenocarcinoma through interacting with p120ctn and suggest that NLBP may function as an oncogene in early stage carcinogenesis of lung adenocarcinoma.