BAP31, a newly defined cancer/testis antigen, regulates proliferation, migration, and invasion to promote cervical cancer progression.
BAP31, a newly defined cancer/testis antigen, regulates proliferation, migration, and invasion to promote cervical cancer progression.
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BAP31 是一种新定义的癌症/睾丸抗原，调节增殖、迁移和侵袭以促进宫颈癌进展。
DOI：
10.1038/s41419-018-0824-2
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发表时间：
2018-07-18
影响因子：
9
通讯作者：
Yang K
中科院分区：
文献类型：
--
作者：
Dang E;Yang S;Song C;Jiang D;Li Z;Fan W;Sun Y;Tao L;Wang J;Liu T;Zhang C;Jin B;Wang J;Yang K
恶性肿瘤通常经历以胚胎基因和原癌基因的过表达为特征的返祖性消退，所述原癌基因包括多种癌症/睾丸抗原（CTA），所述癌症/睾丸抗原是睾丸衍生的并且在体细胞组织中不表达或以痕量表达。基于这一理论，我们建立了一种新的鉴定未知CTA的方法--生精细胞特异性单克隆抗体定义的癌/睾丸抗原（SADA）法。使用SADA方法，我们将BAP 31鉴定为新型CTA，并证实BAP 31表达与几种癌症的进展和转移相关，特别是在宫颈癌中。我们发现BAP 31在I、II和III期宫颈癌患者中显著上调，并且与不良临床结局高度相关。我们进一步证明了BAP 31通过将细胞周期阻滞在G 0/G1期来调节宫颈癌细胞增殖，并且BAP 31的耗尽抑制过度增殖。此外，BAP 31的缺失还通过调节Dreplatin、M-RIP、SPECC 1 L和Nexilin的表达和亚细胞定位，进而影响细胞骨架的组装，抑制宫颈癌细胞的侵袭和迁移。最后，BAP 31的缺失在体内防止宫颈癌进展和转移。这些发现为鉴定新型CTA提供了新方法，并为BAP 31如何调节宫颈癌过度增殖和转移提供了机制见解。
Malignant tumors typically undergo an atavistic regression characterized by the overexpression of embryonic genes and proto-oncogenes, including a variety of cancer/testis antigens (CTAs) that are testis-derived and are not expressed or expressed in trace amounts in somatic tissues. Based on this theory, we established a new method to identify unknown CTAs, the spermatogenic cells-specific monoclonal antibody-defined cancer/testis antigen (SADA) method. Using the SADA method, we identified BAP31 as a novel CTA and confirmed that BAP31 expression is associated with progression and metastasis of several cancers, particularly in cervical cancer. We found that BAP31 was significantly upregulated in stage I, II, and III cervical cancer patients and highly correlated with poor clinic outcomes. We further demonstrated that BAP31 regulates cervical cancer cell proliferation by arresting the cell cycle at the G0/G1 stage and that depletion of BAP31 inhibits hyper-proliferation. Moreover, depletion of BAP31 inhibits cervical cancer cell invasion and migration by regulating the expression and subcellular localization of Drebrin, M-RIP, SPECC1L, and Nexilin, and then affect the cytoskeleton assemblage. Finally, the depletion of BAP31 prevents cervical cancer progression and metastasis in vivo. These findings provide a new method for identifying novel CTAs as well as mechanistic insights into how BAP31 regulates cervical cancer hyper-proliferation and metastasis.
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影响因子：
64.5
作者：
Wang, Bing;Heath-Engel, Hannah;Shore, Gordon C.
通讯作者：
Shore, Gordon C.
影响因子：
21.3
作者：
Geiger, Roger;Andritschke, Daniel;Helenius, Ari
通讯作者：
Helenius, Ari
影响因子：
8.8
作者：
Fujiwara, S.;Wada, H.;Kawada, J.;Kawabata, R.;Takahashi, T.;Fujita, J.;Hirao, T.;Shibata, K.;Makari, Y.;Iijima, S.;Nishikawa, H.;Jungbluth, A. A.;Nakamura, Y.;Kurokawa, Y.;Yamasaki, M.;Miyata, H.;Nakajima, K.;Takiguchi, S.;Nakayama, E.;Mori, M.;Doki, Y.
通讯作者：
Doki, Y.
影响因子：
8.8
作者：
Namba T;Tian F;Chu K;Hwang SY;Yoon KW;Byun S;Hiraki M;Mandinova A;Lee SW
通讯作者：
Lee SW
影响因子：
--
作者：
Gjerstorff MF;Andersen MH;Ditzel HJ
通讯作者：
Ditzel HJ