Rnd3 regulates lung cancer cell proliferation through notch signaling

Yongjun Tang; Chengping Hu; Huaping Yang; Liming Cao; Yuanyuan Li; Pengbo Deng; Li Huang

doi:10.1371/journal.pone.0111897

Rnd3 regulates lung cancer cell proliferation through notch signaling

PLoS One. 2014 Nov 5;9(11):e111897. doi: 10.1371/journal.pone.0111897. eCollection 2014.

Authors

Yongjun Tang¹, Chengping Hu¹, Huaping Yang¹, Liming Cao¹, Yuanyuan Li¹, Pengbo Deng¹, Li Huang¹

Affiliation

¹ Department of Respiratory Medicine, Xiangya Hospital, the Central South University, Changsha, Hunan, P.R. China.

Abstract

Rnd3/RhoE is a small Rho GTPase involved in the regulation of different cell behaviors. Dysregulation of Rnd3 has been linked to tumorigenesis and metastasis. Lung cancers are the leading cause of cancer-related death in the West and around the world. The expression of Rnd3 and its ectopic role in non-small cell lung cancer (NSCLC) remain to be explored. Here, we reported that Rnd3 was down-regulated in three NSCLC cell lines: H358, H520 and A549. The down-regulation of Rnd3 led to hyper-activation of Rho Kinase and Notch signaling. The reintroduction of Rnd3 or selective inhibition of Notch signaling, but not Rho Kinase signaling, blocked the proliferation of H358 and H520 cells. Mechanistically, Notch intracellular domain (NICD) protein abundance in H358 cells was regulated by Rnd3-mediated NICD proteasome degradation. Rnd3 regulated H358 and H520 cell proliferation through a Notch1/NICD/Hes1 signaling axis independent of Rho Kinase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Basic Helix-Loop-Helix Transcription Factors / metabolism
Carcinoma, Non-Small-Cell Lung / genetics
Carcinoma, Non-Small-Cell Lung / metabolism
Cell Line, Tumor
Cell Proliferation
Down-Regulation
Gene Expression
Homeodomain Proteins / metabolism
Humans
Lung Neoplasms / genetics*
Lung Neoplasms / metabolism*
Receptors, Notch / metabolism*
Signal Transduction*
Transcription Factor HES-1
rho GTP-Binding Proteins / genetics*
rho GTP-Binding Proteins / metabolism
rho-Associated Kinases / metabolism

Substances

Basic Helix-Loop-Helix Transcription Factors
Homeodomain Proteins
Receptors, Notch
Transcription Factor HES-1
HES1 protein, human
rho-Associated Kinases
RND3 protein, human
rho GTP-Binding Proteins

Grants and funding

This work was supported by the Key cite of National Clincial Research Center for Respiratory Disease, National Key Scientific & Technology Support Program: Collaborative innovation of Clinical Research for chronic obstructive pulmonary disease and lung cancer, No. 2013BAI09B09. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.