Synergy between truncated c-Met (cyto-Met) and c-Myc in liver oncogenesis: importance of TGF-beta signalling in the control of liver homeostasis and transformation
Authors: Francesco Lozupone
Mauro Piacentini
Laura Amicone
Barbara Costabile
Carlo Della Rocca
Marie Annick Buendia
Marco Tripodi
Olivier Terradillos
Carla Cicchini
Ludovica Calvo
Journal: Oncogene (2002)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: c-Met; Hepatocyte Growth Factor; liver proliferation; transformation; TGF-beta1 signaling
Affiliations: Fondazione Istituto Pasteur-Cenci Bolognetti, Dipartimento di Biotecnologie Cellulari ed Ematologia, Sezione di Genetica Molecolare, Università La Sapienza, 00161, Rome, Italy.

Abstract:  The c-Met tyrosine kinase receptor and its ligand, Hepatocyte Growth Factor/ Scatter Factor, have been implicated in human cancer. We have previously described that the transgenic expression of a truncated form of human c-Met (cyto-Met) in the liver confers resistance to several apoptotic stimuli. Here we show the impact of cyto-Met expression on liver proliferation and transformation. Despite a sixfold increase of hepatocyte proliferation, adult transgenic livers displayed normal size and architecture. We present evidence showing that activation of TGF-beta1 signalling controls the liver mass in cyto-Met mice. The oncogenic potential of cyto-Met was further assessed in the context of c-Myc-induced hepatocarcinogenesis, using WHV/c-Myc transgenic mice. Co-expression of cyto-Met and c-Myc further enhanced hepatocyte proliferation and caused a dramatic acceleration of the Myc-induced tumorigenesis, leading to the emergence of hepatocarcinomas in 3-4-month-old animals. Importantly, the TGF-beta receptor type II expression was strongly downregulated in most tumours, indicating that impairment of TGF-beta1-mediated growth inhibition plays a major role in accelerated neoplastic development. The strong potential of cyto-Met for oncogenic cooperation without direct transforming activity designates cyto-Met mice as an ideal tool for studying the early steps of multistage hepatocarcinogenesis and for identification of prognostic markers of transformation. 

Retracted: No

PubPeer comments:
 Consider this opening passage: ![file] There is no obvious link between Schroedinger and the system of differential equations presented.  Schroedinger just seems to function here as a Worship Word. More importantly, nothing remotely resembling the equations can be found within [Ren (2013)] , who was not concerned with predator-prey dynamics, positivity, uniqueness, boundedness **or** the Hopf bifurcation. Ref [12] is Wang, J., Mai, A., Wang, H.:  Existence and uniqueness of solutions for the Schru00f6dinger integrable boundary value problem . Bound. Value Probl. 2018, 74 (2018). [Recently retracted] for peer-review manipulation and what appears to be papermill behaviour. Ref [9] in the References is Zhang, X., Liu, D., Yan, Z., Zhao, G., Yuan, Y.:  Schru00f6dinger-type identity for Schru00f6dinger free boundary problems . Bound. Value Probl. 2018, 135 (2018) - another exercise in the use of  Schru00f6dinger for invocatory purposes. [I have concerns] . Here the *text* deviates, and we read  Chen and Zhang [9] ... possibly intending to cite [Chen Shang (2017)] , a *different* problematic paper. ---------------------------------------------- The **Abstract**: *In this article we study applications of the Schru00f6dinger-type identity for obtaining transmutations via the fixed point index for nonlinear integral equations. It is possible to derive a wide range of transmutation operators by this method. Classical Riesz transforms are involved in the Schru00f6dinger-type identity method as basic blocks, among them are Fourier, sine and cosine-Fourier, Hankel, Mellin, Laplace, and some generalized transforms. In this paper, we present a modified Schru00f6dinger-type identity for solutions of a class of linear Schru00f6dinger equations with mixed boundary conditions. The techniques used in our proofs are quite different, and most remarkably some of the proofs become simpler and more straightforward. As an application, we obtain the existence and uniqueness of a solution to the stationary Schru00f6dinger equation in the sense of the Weyl law, which advances the recent results obtained in several articles even in a more general setting.* The **Conclusions**: *In this work, we have studied applications of the Schru00f6dinger-type identity for obtaining transmutations via the fixed point index for nonlinear integral equations. It was possible to derive a wide range of transmutation operators by this method. Classical Riesz transforms were involved in the Schru00f6dinger-type identity method as basic blocks, among them are Fourier, sine and cosine-Fourier, Hankel, Mellin, Laplace, and some generalized transforms. In this paper, we presented a modified Schru00f6dinger-type identity for solutions of a class of linear Schru00f6dinger equations with mixed boundary conditions. The techniques used in our proofs were quite different, and most remarkably some of the proofs became simpler and more straightforward. As an application, we obtained the existence and uniqueness of a solution to the stationary Schru00f6dinger equation in the sense of the Weyl law, which advanced the recent results obtained in several articles even in a more general setting.* These agree well, but bear very little relationship to the text separating them. ,