The c-MET oncoprotein: Function, mechanisms of degradation and its targeting by novel anti-cancer agents

Park, Kyung Chan; Richardson, Des R.

doi:10.1016/j.bbagen.2020.129650

Cited by 25 publications

(15 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hence, we propose that UBTD1 impairs EGFR-positive vesicle positioning through a p62/SQSTM1-RNF26 mechanism close to the one described by Jongsma et al [33]. Importantly, this process is presumably not restricted to EGFR since we observe, as anticipated by Jongsma et al [33], similar effects of UBTD1 depletion on other signaling receptors that use the same intracellular routing as EGFR such as c-Met or TGF-β R [40,41]. Although UBTD1 depletion affects p62/SQSTM1 ubiquitination by RNF26, it has a relatively minor impact on P62/SQSTM1-dependent autophagy demonstrating a high specificity toward some E3s rather than for the substrate in the ubiquitination process.…”

Section: Discussionsupporting

confidence: 86%

UBTD1 regulates ceramide balance and endolysosomal positioning to coordinate EGFR signaling

Torrino

Tiroille

Dolfi

et al. 2021

eLife

View full text Add to dashboard Cite

To adapt in an ever-changing environment, cells must integrate physical and chemical signals and translate them into biological meaningful information through complex signaling pathways. By combining lipidomic and proteomic approaches with functional analysis, we have shown that UBTD1 (Ubiquitin domain-containing protein 1) plays a crucial role in both the EGFR (Epidermal Growth Factor Receptor) self-phosphorylation and its lysosomal degradation. On the one hand, by modulating the cellular level of ceramides through ASAH1 (N-Acylsphingosine Amidohydrolase 1) ubiquitination, UBTD1 controls the ligand-independent phosphorylation of EGFR. On the other hand, UBTD1, via the ubiquitination of SQSTM1/p62 (Sequestosome 1) by RNF26 and endolysosome positioning, participates in the lysosomal degradation of EGFR. The coordination of these two ubiquitin-dependent processes contributes to the control of the duration of the EGFR signal. Moreover, we showed that UBTD1 depletion exacerbates EGFR signaling and induces cell proliferation emphasizing a hitherto unknown function of UBTD1 in EGFR-driven human cell proliferation.

show abstract

Section: Discussionsupporting

confidence: 86%

UBTD1 regulates ceramide balance and endolysosomal positioning to coordinate EGFR signaling

Torrino

Tiroille

Dolfi

et al. 2021

eLife

View full text Add to dashboard Cite

show abstract

“…Finally, a combination of α v β 3 -binding c(RGDyK) and a peptide specifically targeting the mesenchymal-epithelial transition factor (c-Met) was reported. The c-Met is overexpressed in a variety of tumors and is associated with invasive cancer growth, increased metastatic potential, proliferation and vascularity [133]. Thus, the concomitant targeting of both c-Met and α v β 3 could result in a higher target visualization sensitivity and specificity compared with using one peptide alone.…”

Section: Heterobivalent Agents Comprising An α V β 3 Integrin-bindingmentioning

confidence: 99%

Current State of Radiolabeled Heterobivalent Peptidic Ligands in Tumor Imaging and Therapy

et al. 2020

View full text Add to dashboard Cite

Over the past few years, an approach emerged that combines different receptor-specific peptide radioligands able to bind different target structures on tumor cells concomitantly or separately. The reason for the growing interest in this special field of radiopharmaceutical development is rooted in the fact that bispecific peptide heterodimers can exhibit a strongly increased target cell avidity and specificity compared to their corresponding monospecific counterparts by being able to bind to two different target structures that are overexpressed on the cell surface of several malignancies. This increase of avidity is most pronounced in the case of concomitant binding of both peptides to their respective targets but is also observed in cases of heterogeneously expressed receptors within a tumor entity. Furthermore, the application of a radiolabeled heterobivalent agent can solve the ubiquitous problem of limited tumor visualization sensitivity caused by differential receptor expression on different tumor lesions. In this article, the concept of heterobivalent targeting and the general advantages of using radiolabeled bispecific peptidic ligands for tumor imaging or therapy as well as the influence of molecular design and the receptors on the tumor cell surface are explained, and an overview is given of the radiolabeled heterobivalent peptides described thus far.

show abstract

“…MACC1 may be highly expressed in esophageal squamous cell carcinoma, and its high expression may be associated with poor prognosis of esophageal carcinoma, but its speci c role and relationship remain to be explored. c-Met is one of the most important receptors and pathways associated with cancer [15] .c-Met tyrosine kinase is a cell surface receptor for hepatocyte growth factor (HGF) and is involved in the regulation of cell proliferation, apoptosis, and migration [16] . Recently, it has been reported that c-Met is involved in many digestive system neoplasm, including gastric cancer, hepatocellular carcinoma, pancreatic cancer, esophageal cancer, and colon and rectal cancers [17] .…”

Section: Introductionmentioning

confidence: 99%

The effect of SOX17, MACC1 and c-Met expression in ESCC on prognosis

Shi

et al. 2021

Preprint

View full text Add to dashboard Cite

Aim: We mainly explored the expression of SOX17, MACC1 and c-Met in esophageal squamous cell carcinoma and their influence on the prognosis of patients.Methods：Expressions of SOX17, MACC1 and c-Met protein in a sample of 232 ESCC and adjacent nontumorous tissues were detected by immunohistochemistry. Their relationships and correlations with clinicopathological features and clinical prognosis were analyzed by SPSS 23.0.Results：SOX17 was associated with Vascular invasion (p=0.017) and Nerve invasion (p=0.014). MACC1 was correlated with Tumor size (p=0.039) and TNM stage (p=0.020).c-Met was significantly associated with hematogenous metastasis (p=0.045). The expression of MACC1 was correlated with c-Met (P<0.001). c-Met expression(p=0.021) were associated with OS. Conclusion: SOX17, MACC1 and c-Met may be new diagnostic targets for esophageal squamous cell carcinoma. c-Met may be a new therapeutic and prognostic target.

show abstract

The c-MET oncoprotein: Function, mechanisms of degradation and its targeting by novel anti-cancer agents

Cited by 25 publications

References 93 publications

UBTD1 regulates ceramide balance and endolysosomal positioning to coordinate EGFR signaling

UBTD1 regulates ceramide balance and endolysosomal positioning to coordinate EGFR signaling

Current State of Radiolabeled Heterobivalent Peptidic Ligands in Tumor Imaging and Therapy

The effect of SOX17, MACC1 and c-Met expression in ESCC on prognosis

Contact Info

Product

Resources

About