Hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) and guanylate kinase 1 (GUK1) are differentially expressed in GH-secreting adenomas

Rocha, Anderson V.; Giorgi, Ricardo Rodrigues; de, Sandra Valeria; Côrrea-Giannella, Maria Lúcia; Fortes, Maria Angela Henriques Zanella; Cavaleiro, Ana Mercedes; Machado, Márcio Carlos; Cescato, Valter Ângelo Sperling; Bronstein, Marcello D.; Giannella-Neto, Daniel

doi:10.1007/s11102-006-9277-1

Cited by 11 publications

(4 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This finding may be consistent with a former report indicating that Hrs is highly expressed in growth hormone-secreting adenoma (49). The spectra of Hrs expression seem to at least partially correlate with that of Wnt signal-related cancers, such as colorectal, gastric, and hepatocellular carcinomas (50).…”

Section: Discussionsupporting

confidence: 92%

Inhibition of Tumor Growth and Metastasis by Depletion of Vesicular Sorting Protein Hrs: Its Regulatory Role on E-Cadherin and β-Catenin

Toyoshima

Tanaka

Aoki³

et al. 2007

Cancer Research

View full text Add to dashboard Cite

Abnormally high signals from receptor tyrosine kinases (RTK) are associated with carcinogenesis, and impaired deactivation of RTKs may also be a mechanism in cancer. Hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) is one of the master regulators that sort activated receptors toward lysosomes and shut down their signals. Hrs contains a ubiquitin-interacting motif and is involved in the endosomal sorting of monoubiquitinated membrane proteins, such as growth factor receptor and E-cadherin. Here, we investigated the role of Hrs in determining the malignancy of cancer cells and discovered that the targeted disruption of Hrs by small interfering RNA effectively attenuated the proliferation, anchorage-independent growth, tumorigenesis, and metastatic potential of HeLa cells in vitro and in vivo. The restoration of Hrs expression increased cell proliferation and anchorage-independent growth in a mouse embryonic fibroblast line established from a Hrs knockout mouse. Further analysis revealed that Hrs depletion was associated with the up-regulation of E-cadherin and reduced B-catenin signaling. The aberrant accumulation of E-cadherin most likely resulted from impaired E-cadherin degradation in lysosomes. These results suggest that Hrs may play a critical role in determining the malignancy of cancer cells by regulating the degradation of E-cadherin. [Cancer Res 2007; 67(11):5162-71]

show abstract

Section: Discussionsupporting

confidence: 92%

Inhibition of Tumor Growth and Metastasis by Depletion of Vesicular Sorting Protein Hrs: Its Regulatory Role on E-Cadherin and β-Catenin

Toyoshima

Tanaka

Aoki³

et al. 2007

Cancer Research

View full text Add to dashboard Cite

show abstract

“…HRS overexpression is known to be associated with malignancy and poor prognosis 5,46 , and previous studies shown an association of several types of human cancer, such as colorectal, gastric, and hepatocellular carcinomas, with a significantly elevated expression of HRS 47,48 , though the underlying related molecular mechanism remains unclear. Additionally, HRS-deficient mice, or mice with double knockout of STAM1 and STAM2 show embryonic mortality 49,50 .…”

Section: Discussionmentioning

confidence: 99%

ROR1 sustains multivesicular endosomes by interacting with HRS and STAM1

Yamaguchi

Yamamoto

Yamazaki

et al. 2020

Preprint

View full text Add to dashboard Cite

The receptor tyrosine kinase-like orphan receptor 1 (ROR1) regulates caveolae formation and caveolae-dependent endocytosis by interacting with caveolae components, which in turn sustains pro-survival signaling toward AKT from multiple RTKs, including EGFR, and MET. We report here a novel function of ROR1 as a scaffold for HRS and STAM1, two essential components of ESCRT-0. The present results show that ROR1 facilitates interactions of HRS and STAM1, thereby preventing the lysosomal degradation of HRS. Furthermore, interaction of ROR1 with STAM1 was found to be required to sustain binding of ROR1 to HRS as well as HRS subcellular localization. Additionally, ROR1 localized in both the limiting membrane and intraluminal vesicles (ILVs) of Rab5-induced multivesicular endosomes (MVEs) containing HRS, CD63, and EEA1 was found to regulate the formation of Rab5-induced MVEs by an association with the GTP-bound form of Rab5 in cancer cells. Notably, ROR1 depletion inhibits CD63-positive MVEs formation and reduces exosomes release. Our findings provide the first evidence that the onco-embryonic antigen receptor ROR1 regulates exosome biogenesis via MVE formation in cancer cells.

show abstract

“…De Rocha et al . found that GUK1 was differentially expressed in metastatic pituitary carcinoma 31 . Hu et al .…”

Section: Resultsmentioning

confidence: 96%

A signal-based method for finding driver modules of breast cancer metastasis to the lung

Yan

Chen

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Tumor metastasis is mainly caused by somatic genomic alterations (SGAs) that perturb pathways regulating metastasis-relevant activities and thus help the primary tumor to adapt to the new microenvironment. Identifying drivers of metastasis, i.e. SGAs, sheds light on the metastasis mechanism and provides guidance for targeted therapy. In this paper, we introduce a novel method to search for SGAs driving breast cancer metastasis to the lung. First, we search for transcriptomic modules with genes that are differentially expressed in breast cell lines with strong metastatic activities to the lung and co-expressed in a large number of breast tumors. Then, for each transcriptomic module, we search for a set of SGA genes (driver modules) such that genes in each driver module carry a common signal regulating the transcriptomic module. Evaluations indicate that many genes in driver modules are indeed related to metastasis, and our methods have identified many new driver candidates. We further choose two novel metastatic driver genes, BCL2L11 and CDH9, for in vitro verification. The wound healing assay reveals that inhibiting either BCL2L11 or CDH9 will enhance the migration of cell lines, which provides evidence that these two genes are suppressors of tumor metastasis.

show abstract

Hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) and guanylate kinase 1 (GUK1) are differentially expressed in GH-secreting adenomas

Cited by 11 publications

References 45 publications

Inhibition of Tumor Growth and Metastasis by Depletion of Vesicular Sorting Protein Hrs: Its Regulatory Role on E-Cadherin and β-Catenin

Inhibition of Tumor Growth and Metastasis by Depletion of Vesicular Sorting Protein Hrs: Its Regulatory Role on E-Cadherin and β-Catenin

ROR1 sustains multivesicular endosomes by interacting with HRS and STAM1

A signal-based method for finding driver modules of breast cancer metastasis to the lung

Contact Info

Product

Resources

About