Correction: Protein 4.1N acts as a potential tumor suppressor linking PP1 to JNK-c-Jun pathway regulation in NSCLC.

[This corrects the article DOI: 10.18632/oncotarget.6312.].

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

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 (p16INK4A -pRb pathway), and up-regulation of many members of the Wnt gene family. In particular, 4.1B-/- iMEFs exhibited nuclear accumulation of ß-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. © 2016 Wiley Periodicals, Inc.

Protein 4.1N acts as a potential tumor suppressor linking PP1 to JNK-c-Jun pathway regulation in NSCLC.

Protein 4.1N is a member of protein 4.1 family and has been recognized as a potential tumor suppressor in solid tumors. Here, we aimed to investigate the role and mechanisms of 4.1N in non-small cell lung cancer (NSCLC). We confirmed that the expression level of 4.1N was inversely correlated with the metastatic properties of NSCLC cell lines and histological grade of clinical NSCLC tissues. Specific knockdown of 4.1N promoted tumor cell proliferation, migration and adhesion in vitro, and tumor growth and metastasis in mouse xenograft models. Furthermore, we identified PP1 as a novel 4.1N-interacting molecule, and the FERM domain of 4.1N mediated the interaction between 4.1N and PP1. Further, ectopic expression of 4.1N could inactivate JNK-c-Jun signaling pathway through enhancing PP1 activity and interaction between PP1 and p-JNK. Correspondingly, expression of potential downstream metastasis targets (ezrin and MMP9) and cell cycle targets (p53, p21 and p19) of JNK-c-Jun pathway were also regulated by 4.1N. Our data suggest that down-regulation of 4.1N expression is a critical step for NSCLC development and that repression of JNK-c-Jun signaling through PP1 is one of the key anti-tumor mechanisms of 4.1N.