The Adhesion GPCR CD97/ADGRE5 inhibits apoptosis

Hsiao, Cheng-Chih; Keysselt, K; Chen, Hsin‐Yi; Sittig, Doreen; Hamann, Jörg; Lin, Hsi‐Hsien; Aust, Gabriela

doi:10.1016/j.biocel.2015.06.007

Cited by 20 publications

(16 citation statements)

References 43 publications

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“…In thyroid and prostate cancer cells, CD97 amplifies LPAR1 signaling to promote tumor progression in a Rho-dependent fashion (30,43). CD97 has also been shown to inhibit programmed tumor cell death (31). All these previous findings are well aligned with the mechanistic model we propose in which the functional impact of edited miR-379-5p is at least partially due to its acquired ability to target CD97, thereby inhibiting proliferation and increasing apoptosis.…”

Section: Discussionsupporting

confidence: 73%

“…This gene has been reported to be induced or upregulated in a variety of human cancers (27)(28)(29)(30); the overexpression of CD97 was found to enhance local tumor growth in immune-deficient mice (30). In addition, shRNA-mediated knockdown of CD97 has been shown to increase caspase-mediated apoptosis (31,32). Clinically, high expression of CD97 correlates with worse patient survival times across cancer types (Supplemental Figure 6).…”

Section: Resultsmentioning

confidence: 96%

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A-to-I–edited miRNA-379-5p inhibits cancer cell proliferation through CD97-induced apoptosis

Wang

Mojumdar

et al. 2019

Journal of Clinical Investigation

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Section: Discussionsupporting

confidence: 73%

Section: Resultsmentioning

confidence: 96%

A-to-I–edited miRNA-379-5p inhibits cancer cell proliferation through CD97-induced apoptosis

Wang

Mojumdar

et al. 2019

Journal of Clinical Investigation

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“…Tumor buds possess an anti-apoptotic behavior ( 31 ). In line herewith, CD97 inhibits apoptosis of tumor cells ( 32 ). High CD97 expression in tumor buds at the invasive front implicated that CD97 might be a direct β-catenin/TCF target gene in the deregulated canonical Wnt-pathway of colorectal cancers.…”

Section: Discussionsupporting

confidence: 62%

The Interaction of CD97/ADGRE5 With β-Catenin in Adherens Junctions Is Lost During Colorectal Carcinogenesis

et al. 2018

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The adhesion G-protein-coupled receptor CD97/ADGRE5 is present in adherens junctions of human normal intestinal cells and upregulated in colorectal carcinomas. Here, we examined whether CD97 directly interacts with junctional proteins in normal and malignant colorectal tissue. We identified an association of CD97 with β-catenin using a proximity ligation assay and confirmed the interaction between both endogenous proteins at the biochemical level by co-immunoprecipitation in human and mouse tissues and cell lines. Glutathione S-transferase-pulldown revealed that CD97 binds β-catenin through its seven-span transmembrane/intracellular domain(s). To study tumor-associated changes in the interaction of CD97 and β-catenin in situ, we quantified and correlated both proteins at the membrane, and in the cytoplasm and nuclei of colorectal carcinomas and their corresponding normal tissues (n = 111). In normal colon, membranous levels of CD97 and β-catenin correlated strongly (p < 0.0001). To some degree both molecules disappeared in carcinomas simultaneously from the membrane of tumor cells (p = 0.017). CD97 accumulated in the cytoplasm, whereas β-catenin emerged in the cytoplasm and nuclei. CD97 and β-catenin levels in the cytoplasm correlated well (p < 0.0001). Irrespective of their subcellular localization, interaction of CD97 with β-catenin in tumor cells was also restricted to the cell contacts. Accordingly, CD97 did not regulate β-catenin-dependent TCF-mediated transcriptional activity. In summary, while CD97 and β-catenin interact in adherens junctions, their interaction is lost and both molecules follow different functional paths inside tumor cells.

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“…Downregulation of ADGRL4 (ELTD1) by microRNA-139-5p leads to an inhibition of glioblastoma cell proliferation in vitro [103]. CD97 protects fibrosarcoma HT1080 and cervical HeLa cancer cell lines from serum starvation- and staurosporine-induced intrinsic apoptosis [104]. …”

Section: Biological Functions Of Adhesion Gpcrs In Cancermentioning

confidence: 99%

Adhesion GPCRs in Tumorigenesis

Aust

Zhu

et al. 2016

Handbook of Experimental Pharmacology

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Alterations in the homeostasis of several adhesion GPCRs (aGPCRs) have been observed in cancer. The main cellular functions regulated by aGPCRs are cell adhesion, migration, polarity, and guidance, which are all highly relevant to tumor cell biology. Expression of aGPCRs can be induced, increased, decreased, or silenced in the tumor or in stromal cells of the tumor microenvironment, including fibroblasts and endothelial and/or immune cells. For example, ADGRE5 (CD97) and ADGRG1 (GPR56) show increased expression in many cancers, and initial functional studies suggest that both are relevant for tumor cell migration and invasion. aGPCRs can also impact the regulation of angiogenesis by releasing soluble fragments following the cleavage of their extracellular domain (ECD) at the conserved GPCR-proteolytic site (GPS) or other more distal cleavage sites as typical for the ADGRB (BAI) family. Interrogation of in silico cancer databases suggests alterations in other aGPCR members and provides the impetus for further exploration of their potential role in cancer. Integration of knowledge on the expression, regulation, and function of aGPCRs in tumorigenesis is currently spurring the first preclinical studies to examine the potential of aGPCR or the related pathways as therapeutic targets.

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The Adhesion GPCR CD97/ADGRE5 inhibits apoptosis

Cited by 20 publications

References 43 publications

A-to-I–edited miRNA-379-5p inhibits cancer cell proliferation through CD97-induced apoptosis

A-to-I–edited miRNA-379-5p inhibits cancer cell proliferation through CD97-induced apoptosis

The Interaction of CD97/ADGRE5 With β-Catenin in Adherens Junctions Is Lost During Colorectal Carcinogenesis

Adhesion GPCRs in Tumorigenesis

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