Knockout of 4.1B triggers malignant transformation in SV40T-immortalized mouse embryo fibroblast cells

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• 作者：Zi Wang ; Jingxin Zhang ; Yayue Zeng ; Shuming Sun ; Ji Zhang ; Bin Zhang ; Min Zhu ; Ruoyun Ouyang ; Bianyin Ma ; Mao Ye ; Xiuli An and Jing Liu
• 刊名：Molecular Carcinogenesis
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：56
• 期：2
• 页码：538-549
• 全文大小：7067K
• ISSN：1098-2744

文摘

Protein 4.1B deficiency has been found to promote the tumor development; however, whether 4.1B deficiency participates in malignant transformation is unknown. In this study, we demonstrated that 4.1B gene deletion was sufficient to transform SV40T antigen-immortalized mouse embryonic fibroblasts (iMEFs), as reflected by the ability of 4.1B^{−/−}iMEFs to growth in the environments that were growth restrictive for 4.1B^+/+iMEFs and to form tumors in nude mice, whereas 4.1B^+/+iMEFs were unable to form tumors in vivo. The histological examination revealed that the tumors generated by 4.1B^{−/−} iMEFs were desmoid tumors with features of local invasion. Moreover, loss of 4.1B significantly accelerated cell cycle progression, accompanied by activation of typical proto-oncogene ERK, AKT, and the G1/S regulatory pathway (p16^INK4A-pRb pathway), and up-regulation of many members of the Wnt gene family. In particular, 4.1B^{−/−} iMEFs exhibited nuclear accumulation of β-catenin, which is an indicator for desmoid tumor, with down-regulation of E-cadherin expression and up-regulation of snail, zeb1, and vimentin expression, indicating that EMT potentially occurred in transformed 4.1B^{−/−} iMEFs. Moreover, we showed that 4.1B interacted with E-cadherin in MEF cells. Thus, our study provides previously unidentified roles and mechanisms of 4.1B in cellular transformation.