A role for TAZ in migration, invasion, and tumorigenesis of breast cancer cells.
TAZ (WWTR1), identified as a 14-3-3 binding protein with a PDZ binding motif, modulates mesenchymal stem cell differentiation. We now show that TAZ plays a critical role in the migration, invasion, and tumorigenesis of breast cancer cells. TAZ is conspicuously expressed in human breast cancer cell lines in which its expression levels generally correlate with the invasiveness of cancer cells. Overexpression of TAZ in low-expressing MCF10A cells causes morphologic changes characteristic of cell transformation and promotes cell migration and invasion. Conversely, RNA interference-mediated knockdown of TAZ expression in MCF7 and Hs578T cells reduces cell migration and invasion. TAZ knockdown in MCF7 cells also retards anchorage-independent growth in soft agar and tumorigenesis in nude mice. Significantly, TAZ is overexpressed in approximately 20% of breast cancer samples. These results indicate that TAZ plays a role in the migration, invasion, and tumorigenesis of breast cancer cells and thus presents a novel target for the detection and treatment of breast cancer.
Chan
Siew Wee
SW
Cancer and Developmental Cell Biology Division, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Lim
Chun Jye
CJ
Guo
Ke
K
Ng
Chee Peng
CP
Lee
Ian
I
Hunziker
Walter
W
Zeng
Qi
Q
Hong
Wanjin
W
D048948:14-3-3 Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D003001:Cloning, Molecular; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000502:physiology*; D011506:Proteins / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D048948:14-3-3 Proteins; D048868:Adaptor Proteins, Signal Transducing; D009363:Neoplasm Proteins; D011506:Proteins; D012334:RNA, Neoplasm; D015534:Trans-Activators; D014157:Transcription Factors; C517794:Wwtr1 protein, mouse; D000217:Acyltransferases; C486363:tafazzin protein, mouse; C108675:TAFAZZIN protein, human