Tumor Suppressor Activity of Selenbp1, a Direct Nkx2-1 Target, in Lung Adenocarcinoma

Molecular Cancer Research : MCR
Deborah CaswellMonte M Winslow

Abstract

The Nkx2-1 transcription factor promotes differentiation of lung epithelial lineages and suppresses malignant progression of lung adenocarcinoma. However, targets of Nkx2-1 that limit tumor growth and progression remain incompletely understood. Here, direct Nkx2-1 targets are identified whose expression correlates with Nkx2-1 activity in human lung adenocarcinoma. Selenium-binding protein 1 (Selenbp1), an Nkx2-1 effector that limits phenotypes associated with lung cancer growth and metastasis, was investigated further. Loss- and gain-of-function approaches demonstrate that Nkx2-1 is required and sufficient for Selenbp1 expression in lung adenocarcinoma cells. Interestingly, Selenbp1 knockdown also reduced Nkx2-1 expression and Selenbp1 stabilized Nkx2-1 protein levels in a heterologous system, suggesting that these genes function in a positive feedback loop. Selenbp1 inhibits clonal growth and migration and suppresses growth of metastases in an in vivo transplant model. Genetic inactivation of Selenbp1, using CRISPR/Cas9, also enhanced primary tumor growth in autochthonous lung adenocarcinoma mouse models. Collectively, these data demonstrate that Selenbp1 is a direct target of Nkx2-1, which inhibits lung adenocarcinoma growth ...Continue Reading

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Citations

Jul 17, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chuanxin LiuWeisan Chen
May 12, 2019·Neuro-oncology·Michail-Dimitrios PapaioannouPhedias Diamandis
Jun 9, 2020·The Prostate·Mostafa ElhodakyAlan M Diamond
May 31, 2019·Scientific Reports·Cody A PhelpsDavid Mu
Nov 8, 2018·International Journal of Molecular Sciences·Mostafa Elhodaky, Alan M Diamond
Apr 15, 2021·Proceedings of the National Academy of Sciences of the United States of America·Najla KfouryJoshua B Rubin
Mar 1, 2020·Annual Review of Cancer Biology·Tuomas Tammela, Julien Sage
Jan 12, 2022·Cellular and Molecular Life Sciences : CMLS·Peiyan ZhengBaoqing Sun

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