Reactivation of developmentally expressed p63 isoforms predisposes to tumor development and progression.
Genes that are active during normal development are frequently reactivated during neoplastic transformation. We now report that developmentally expressed TAp63 isoforms are frequently reactivated in human squamous cell carcinomas. To determine the consequences of TAp63 reactivation, we induced TAp63alpha expression during chemically-induced skin carcinogenesis. Deregulated TAp63alpha expression dramatically accelerated tumor development and progression, frequently resulting in epithelial-mesenchymal transitions to spindle cell carcinomas and lung metastases. Consistent with this observation, we detected high levels of Twist and N-cadherin in tumors overexpressing TAp63alpha. Thus, as observed for other developmental pathways, aberrant reactivation of TAp63 predisposes to tumor development and progression.
Koster
Maranke I
MI
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Lu
Shi-Long
SL
White
Lisa D
LD
Wang
Xiao-Jing
XJ
Roop
Dennis R
DR
D000818:Animals; D015820:Cadherins; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D042822:Genomic Instability; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics*; D020033:Protein Isoforms; D011519:Proto-Oncogenes / Q000502:physiology*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics*; D051879:Twist-Related Protein 1 / Q000096:biosynthesis / Q000235:genetics
C081876:CKAP4 protein, human; D015820:Cadherins; C489083:Cdh2 protein, mouse; D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D015534:Trans-Activators; C486419:Trp63 protein, mouse; D051879:Twist-Related Protein 1