Role of cMET in the Development and Progression of Colorectal Cancer

Samamé Pérez-Vargas, Juan Carlos; Biondani, Pamela; Maggi, Claudia; Gariboldi, Manuela; Gloghini, Annunziata; Inno, Alessandro; Volpi, Chiara Costanza; Gualeni, Ambra Vittoria; Bartolomeo, Maria di; Braud, Filippo de; Castano, Alessandra; Bossi, Ilaria; Pietrantonio, Filippo
September 2013
International Journal of Molecular Sciences;Sep2013, Vol. 14 Issue 9, p18056
Academic Journal
Mesenchymal-epithelial transition (MET) is a member of a distinct subfamily of heterodimeric receptor tyrosine kinase receptors that specifically binds the hepatocyte growth factor (HGF). Binding to HGF leads to receptor dimerization/multimerization and phosphorylation, resulting in its catalytic activation. MET activation drives the malignant progression of several tumor types, including colorectal cancer (CRC), by promoting signaling cascades that mainly result in alterations of cell motility, survival, and proliferation. MET is aberrantly activated in many human cancers through various mechanisms, including point mutations, gene amplification, transcriptional up-regulation, or ligand autocrine loops. MET promotes cell scattering, invasion, and protection from apoptosis, thereby acting as an adjuvant pro-metastatic gene for many tumor types. In CRC, MET expression confers more aggressiveness and worse clinical prognosis. With all of this rationale, inhibitors that target the HGF/MET axis with different types of response have been developed. HGF and MET are new promising targets to understand the pathogenesis of CRC and for the development of new, targeted therapies.


Related Articles

  • MACC1 as a Prognostic Biomarker for Early-Stage and AFP-Normal Hepatocellular Carcinoma Xie, Chan; Wu, Jueheng; Yun, Jingping; Lai, Jiaming; Yuan, Yunfei; Gao, Zhiliang; Li, Mengfeng; Li, Jun; Song, Libing // PLoS ONE;May2013, Vol. 8 Issue 5, p1 

    Background: The metastasis-associated in colon cancer 1 gene (MACC1) has been found to be associated with cancer development and progression. The aim of this study was to investigate the prognostic value of MACC1 in early-stage and AFP-normal hepatocellular carcinoma (HCC). Methods: mRNA and...

  • Activated ras and ret oncogenes induce over-expression of c-met (hepatocyte growth factor receptor) in human thyroid epithelial cells. Ivan, Mircea; Bond, Jane A; Prat, Maria; Comoglio, Paolo Maria; Wynford-Thomas, David // Oncogene;5/22/97, Vol. 14 Issue 20, p2417 

    Hepatocyte Growth Factor (HGF) receptor, encoded by the protooncogene c-met, is overexpressed in many human tumours, including those of thyroid epithelium. The absence in most cases of any primary structural abnormality of the met gene suggests that overexpression is secondary to mutation of...

  • Hepatocyte growth factor accelerates restitution of intestinal epithelial cells. Nishimura, Shuji; Takahashi, Morio; Ota, Shinichi; Hirano, Masanori; Hiraishi, Hideyuki; Nishimura, S; Takahashi, M; Ota, S; Hirano, M; Hiraishi, H // Journal of Gastroenterology;1998, Vol. 33 Issue 2, p172 

    Many cytokines are involved in the repair of damaged tissue, and one of these, hepatocyte growth factor (HGF), is involved not only with liver regeneration but also in the repair of other tissues. To investigate the importance of HGF in the repair of the small intestine, we evaluated its effect...

  • Hepatocyte growth factor modulates motility and invasiveness of ovarian carcinomas via Ras-mediated pathway. Ueoka, Y; Kato, K; Kuriaki, Y; Horiuchi, S; Terao, Y; Nishida, J; Ueno, H; Wake, N // British Journal of Cancer;2/15/2000, Vol. 82 Issue 4, p891 

    Hepatocyte growth factor (HGF) is a multifunctional growth factor which has pleiotrophic biological effects on epithelial cells such as proliferation, motogenesis, invasiveness and morphogenesis. Peritoneal dissemination is critical for the progression of ovarian cancer, and our study revealed...

  • mTORC1-mediated translational elongation limits intestinal tumour initiation and growth. Faller, William J.; Jackson, Thomas J.; Knight, John R. P.; Ridgway, Rachel A.; Jamieson, Thomas; Karim, Saadia A.; Jones, Carolyn; Radulescu, Sorina; Huels, David J.; Myant, Kevin B.; Dudek, Kate M.; Casey, Helen A.; Scopelliti, Alessandro; Cordero, Julia B.; Vidal, Marcos; Pende, Mario; Ryazanov, Alexey G.; Sonenberg, Nahum; Meyuhas, Oded; Hall, Michael N. // Nature;1/22/2015, Vol. 517 Issue 7535, p497 

    Inactivation of APC is a strongly predisposing event in the development of colorectal cancer, prompting the search for vulnerabilities specific to cells that have lost APC function. Signalling through the mTOR pathway is known to be required for epithelial cell proliferation and tumour growth,...

  • The serine protease inhibitor serpinE2 is a novel target of ERK signaling involved in human colorectal tumorigenesis. Bergeron, Sébastien; Lemieux, Etienne; Durand, Véronique; Cagnol, Sébastien; Carrier, Julie C.; Lussier, Jacques G.; Boucher, Marie-Josée; Rivard, Nathalie // Molecular Cancer;2010, Vol. 9, p271 

    Background: Among the most harmful of all genetic abnormalities that appear in colorectal cancer (CRC) development are mutations of KRAS and its downstream effector BRAF as they result in abnormal extracellular signal-related kinase (ERK) signaling. In a previous report, we had shown that...

  • The receptor tyrosine kinase Axl is an essential regulator of prostate cancer proliferation and tumor growth and represents a new therapeutic target. Paccez, J D; Vasques, G J; Correa, R G; Vasconcellos, J F; Duncan, K; Gu, X; Bhasin, M; Libermann, T A; Zerbini, L F // Oncogene;2/7/2013, Vol. 32 Issue 6, p689 

    Deregulation of the receptor tyrosine kinase Axl has been implicated in the progression of several human cancers. However, the role of Axl in prostate cancer remains poorly understood, and the therapeutic efficacy of Axl targeting remains untested. In this report we identified Axl as a new...

  • Hepatocyte growth factor in invasive growth of carcinomas. Desiderio, M. A. // Cellular & Molecular Life Sciences;Jun2007, Vol. 64 Issue 11, p1341 

    Hepatocyte growth factor is a multifunctional cytokine of the tumor microenvironment. An important advance in the knowledge of cancer progression has been the appreciation that the tumor invasive phenotype is strongly influenced by microenvironmental stimuli. Malignant tumor cells recruit...

  • Expression of Hepatocyte Growth Factor Activator Inhibitor Type 1 in Human Hepatocellular Carcinoma and Postoperative Outcomes. Funagayama, Mayumi; Kondo, Kazuhiro; Chijiiwa, Kazuo; Kataoka, Hiroaki // World Journal of Surgery;Jul2010, Vol. 34 Issue 7, p1563 

    Hepatocyte growth factor activator inhibitor type 1 (HAI-1), one of the Kunitz-type serine protease inhibitors, has an important role in cancer progression through regulation of the activity of hepatocyte growth factor. HAI-1 is expressed in hepatocellular carcinoma (HCC) to various degrees....


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics