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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Carcinogenesis
2014 ; 35
(11
): 2602-10
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gab.com Text
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English Wikipedia
Concerted loss of TGF?-mediated proliferation control and E-cadherin disrupts
epithelial homeostasis and causes oral squamous cell carcinoma
#MMPMID25233932
Andl T
; Le Bras GF
; Richards NF
; Allison GL
; Loomans HA
; Washington MK
; Revetta F
; Lee RK
; Taylor C
; Moses HL
; Andl CD
Carcinogenesis
2014[Nov]; 35
(11
): 2602-10
PMID25233932
show ga
Although the etiology of squamous cell carcinomas of the oral mucosa is well
understood, the cellular origin and the exact molecular mechanisms leading to
their formation are not. Previously, we observed the coordinated loss of
E-cadherin (CDH1) and transforming growth factor beta receptor II (TGFBR2) in
esophageal squamous tumors. To investigate if the coordinated loss of Cdh1 and
Tgfbr2 is sufficient to induce tumorigenesis in vivo, we developed two mouse
models targeting ablation of both genes constitutively or inducibly in the
oral-esophageal epithelium. We show that the loss of both Cdh1 and Tgfbr2 in both
models is sufficient to induce squamous cell carcinomas with animals succumbing
to the invasive disease by 18 months of age. Advanced tumors have the ability to
invade regional lymph nodes and to establish distant pulmonary metastasis. The
mouse tumors showed molecular characteristics of human tumors such as
overexpression of Cyclin D1. We addressed the question whether TGF? signaling may
target known stem cell markers and thereby influence tumorigenesis. From our
mouse and human models, we conclude that TGF? signaling regulates key aspects of
stemness and quiescence in vitro and in vivo. This provides a new explanation for
the importance of TGF? in mucosal homeostasis.
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