N-cadherin gene expression in prostate carcinoma is modulated by integrin-dependent nuclear translocation of Twist1

• Published in: Cancer research (Chicago, Ill.) Vol. 66; no. 7; pp. 3365 - 3369
• Main Authors: ALEXANDER, Nelson R, TRAN, Nhan L, REKAPALLY, Harish, SUMMERS, Carol E, GLACKIN, Carlotta, HEIMARK, Ronald L
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.04.2006
• Subjects: Antineoplastic agents; Biological and medical sciences; Cadherins - biosynthesis; Cadherins - genetics; Cell Adhesion - physiology; Cell Line, Tumor; Cell Nucleus - metabolism; E-Box Elements; Fibronectins - metabolism; Gene Expression Regulation, Neoplastic; Gynecology. Andrology. Obstetrics; Humans; Integrin beta1 - metabolism; Introns; Male; Male genital diseases; Medical sciences; Nephrology. Urinary tract diseases; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Pharmacology. Drug treatments; Promoter Regions, Genetic; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; RNA, Small Interfering - genetics; Transcriptional Activation; Tumors; Tumors of the urinary system; Twist-Related Protein 1 - genetics; Twist-Related Protein 1 - metabolism; Urinary tract. Prostate gland; Chromosomal aberration; Prostate carcinoma; Urinary system disease; Prostate disease; Cell adhesion molecule; Malignant tumor; Cadherin; Gene expression; Integrin; Cytogenetics; Abnormal chromosome; Male genital diseases; Prostate cancer; Chromosome translocation
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-05-3401

The gain of N-cadherin expression in carcinomas has been shown to be important in the regulation of cell migration, invasion, and survival. Here, we show that N-cadherin mRNA expression in PC-3 prostate carcinoma cells is dependent on beta(1) integrin-mediated cell adhesion to fibronectin and the basic helix-loop-helix transcription factor Twist1. Depletion of Twist1 mRNA by small interfering RNA resulted in decreased expression of both Twist1 and N-cadherin and the inhibition of cell migration. Whereas Twist1 gene expression was independent of beta(1) integrin-mediated adhesion, Twist1 protein failed to accumulate in the nuclei of cells cultured in anchorage-independent conditions. The increased nuclear accumulation of Twist1 following cell attachment was suppressed by treatment with an inhibitor of Rho kinase or a beta(1) integrin neutralizing antibody. The effect of Twist1 on induction of N-cadherin mRNA required an E-box cis-element located within the first intron (+2,627) of the N-cadherin gene. These data raise the possibility that integrin-mediated adhesion to interstitial matrix proteins during metastasis differentially regulates the nuclear/cytoplasmic translocation and DNA binding of Twist1, activating N-cadherin transcription.