EMT and induction of miR-21 mediate metastasis development in Trp53-deficient tumours

被引：76

作者：

Bornachea, Olga ^{[1
]}

Santos, Mirentxu ^{[1
]}

Belen Martinez-Cruz, Ana ^{[1
]}

Garcia-Escudero, Ramon ^{[1
]}

Duenas, Marta ^{[1
]}

Costa, Clotilde ^{[1
]}

Segrelles, Carmen ^{[1
]}

Lorz, Corina ^{[1
]}

Buitrago, Agueda ^{[1
]}

Saiz-Ladera, Cristina ^{[1
]}

Agirre, Xabier ^{[2
]}

Grande, Teresa ^{[3
]}

Paradela, Beatriz ^{[1
]}

Maraver, Antonio ^{[4
]}

Ariza, Jose M. ^{[1
]}

Prosper, Felipe ^{[2
]}

Serrano, Manuel ^{[4
]}

Sanchez-Cespedes, Montse ^{[5
]}

Paramio, Jesus M. ^{[1
]}

机构：

[1] CIEMAT, Mol Oncol Unit, E-28040 Madrid, Spain

[2] Univ Navarra, Ctr Appl Med Res, E-31008 Pamplona, Spain

[3] CIEMAT, Unit Med Applicat, E-28040 Madrid, Spain

[4] Spanish Natl Canc Res Ctr CNIO, Tumour Suppress Grp, E-28029 Madrid, Spain

[5] Hosp Duran i Reynals, IDIBELL, PEBC, Genes & Canc Grp, Barcelona 08907, Spain

来源：

SCIENTIFIC REPORTS | 2012年 / 2卷

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; IN-VIVO; TRANSCRIPTIONAL REGULATION; MOLECULAR DETERMINANTS; COORDINATE REGULATION; EXPRESSION SIGNATURE; LUNG-CANCER; MOUSE MODEL; P53; CELL;

D O I：

10.1038/srep00434

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Missense mutations in TP53 gene promote metastasis in human tumours. However, little is known about the complete loss of function of p53 in tumour metastasis. Here we show that squamous cell carcinomas generated by the specific ablation of Trp53 gene in mouse epidermis are highly metastatic. Biochemical and genome-wide mRNA and miRNA analyses demonstrated that metastases are associated with the early induction of epithelial-mesenchymal transition (EMT) and deregulated miRNA expression in primary tumours. Increased expression of miR-21 was observed in undifferentiated, prometastatic mouse tumours and in human tumours characterized by p53 mutations and distant metastasis. The augmented expression of miR-21, mediated by active mTOR and Stat3 signalling, conferred increased invasive properties to mouse keratinocytes in vitro and in vivo, whereas blockade of miR-21 in a metastatic spindle cell line inhibits metastasis development. Collectively these data identify novel molecular mechanisms leading to metastasis in vivo originated by p53 loss in epithelia.

引用

页数：12

共 89 条

[1] A Mutant-p53/Smad Complex Opposes p63 to Empower TGFβ-Induced Metastasis [J].