C-Cbl protein in human cancer tissues is frequently tyrosine phosphorylated in a tumor-specific manner.

Kamei, Tatsuya; Machida, Kazuya; Nimura, Yuji; Senga, Takeshi; Yamada, I; Yoshii, Satoru; Matsuda, Satoru; Hamaguchi, Michinari

doi:10.3892/ijo.17.2.335

Cited by 10 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Activation of c-Src kinase was found frequently in carcinoma of the breast, colorectum and stomach [2,16,24]. In various tumor tissues, Cbl was tyrosine phosphorylated in a tumor-specific manner [10], suggesting that Cbl signaling may play an important role in tumorigenesis of various human cancers. It was reported that deregulated tyrosine phosphorylation of Cbl promotes leukemogenesis and that this can be achieved by mutation of Cbl or by an activated form of the tyrosine kinase abl [1].…”

Section: Discussionmentioning

confidence: 99%

Expression of Cbl linking with the epidermal growth factor receptor system is associated with tumor progression and poor prognosis of human gastric carcinoma

et al. 2004

View full text Add to dashboard Cite

Cbl proteins play important roles in downregulation of growth factor receptors by acting as ubiquitin ligases and multi-adapter proteins. Ligand-induced desensitization of the epidermal growth factor receptor (EGFR) has been shown to be controlled by Cbl. In the present study, we examined the expression of Cbl in gastric carcinomas and studied the correlation of Cbl expression with clinicopathological characteristics as well as EGFR expression. Cbl protein was expressed in 67% (82/122) of gastric carcinomas, and diffuse expression of Cbl was detected in 29% (35/122) of the cases. The incidence of cases with diffuse expression of Cbl was significantly higher in advanced cases (28/70, 40%) than in early cases (7/52, 14%) (P=0.0010). Diffuse expression of Cbl was significantly associated with metastasis of tumor cells in lymph nodes (P=0.0318). Diffuse expression of EGFR was significantly associated with depth of invasion (P=0.0057), lymph-node metastasis (P=0.0371) and tumor stages (P=0.0278). As the grades of Cbl expression became stronger, the cases with diffuse EGFR expression increased, the positive correlation being significant (P=0.049). All the cases with diffuse expression of Cbl and EGFR were found to show nodal metastasis and to be at an advanced stage. Moreover, the prognosis of the patients with synchronous diffuse expression of Cbl and EGFR was significantly poorer than that of the patients negative for Cbl and focal or negative for EGFR (P=0.0086). The expression of Cbl protein was clearly induced in gastric carcinoma cell lines by transforming growth factor-alpha treatment. These results suggest that Cbl in connection with the EGFR system may be associated with stomach carcinogenesis, invasion and metastasis. Cbl may serve as a novel molecular marker for aggressive gastric carcinoma.

show abstract

Section: Discussionmentioning

confidence: 99%

Expression of Cbl linking with the epidermal growth factor receptor system is associated with tumor progression and poor prognosis of human gastric carcinoma

et al. 2004

View full text Add to dashboard Cite

show abstract

“…Constitutive tyrosine phosphorylation of c-Cbl has been found in various specimens and cell lines from cancers. 29 Tyrosine 700, 731, and 774 have been identified as major phosphorylation sites by receptor and nonreceptor PTKs. 19 Phosphorylation of tyrosine 731 provides a docking site for p85-PI3K, which generates specific inositol phospholipids and recruits Akt to the cell membrane for its activation.…”

Section: Tang Et Al Role Of C-cbl In Vascular Remodelingmentioning

confidence: 99%

Suppression of c-Cbl Tyrosine Phosphorylation Inhibits Neointimal Formation in Balloon-Injured Rat Arteries

et al. 2008

View full text Add to dashboard Cite

Background-c-Cbl, a ubiquitously expressed protooncogene, is tyrosine phosphorylated in response to a variety of stimuli, including growth factors such as platelet-derived growth factor (PDGF), and consequently activates signaling proteins such as phosphatidylinositol-3 kinase (PI3K) and Akt. In the present study, we examined the role of c-Cbl tyrosine phosphorylation in vascular injury. Methods and Results-Western blotting showed that the tyrosine phosphorylation of c-Cbl was increased in ballooninjured rat carotid arteries and in cultured smooth muscle cells on stimulation by PDGF-BB, followed by the activations of Akt and the mammalian target of rapamycin. Adenovirus-mediated overexpression of a c-Cbl mutant that ablates the major tyrosine phosphorylation sites attenuated the Akt and the mammalian target of rapamycin activation and decreased the proliferation and migration of smooth muscle cells in response to PDGF-BB or fibroblast growth factor. These effects could be reversed by constitutively active PI3K or Akt, suggesting that c-Cbl phosphorylation promotes the PDGF-BB-induced proliferation and migration of smooth muscle cells through the PI3K/Akt pathways. In addition, overexpression of c-Cbl-m increased the ubiquitination of the PDGF and fibroblast growth factor receptors. Importantly, in balloon-injured rat carotid arteries, local delivery of c-Cbl-m reduced the phosphorylation of Akt and the mammalian target of rapamycin, inhibited the migration and proliferation of smooth muscle cells, and prevented neointimal hyperplasia. Conclusions-Our

show abstract

“…Finally, various cell lines derived from cancer and surgical specimens demonstrate constitutive tyrosine phosphorylation of c-Cbl (Kamei et al, 2000). This increase appears to be somewhat speci®c to colon and renal cancer.…”

Section: Tyrosine Phosphorylation Of Cbl Proteinsmentioning

confidence: 93%

Beyond the RING: CBL proteins as multivalent adapters

et al. 2001

View full text Add to dashboard Cite

C-Cbl protein in human cancer tissues is frequently tyrosine phosphorylated in a tumor-specific manner.

Cited by 10 publications

References 0 publications

Expression of Cbl linking with the epidermal growth factor receptor system is associated with tumor progression and poor prognosis of human gastric carcinoma

Expression of Cbl linking with the epidermal growth factor receptor system is associated with tumor progression and poor prognosis of human gastric carcinoma

Suppression of c-Cbl Tyrosine Phosphorylation Inhibits Neointimal Formation in Balloon-Injured Rat Arteries

Beyond the RING: CBL proteins as multivalent adapters

Contact Info

Product

Resources

About