APLN/APLNR Signaling Controls Key Pathological Parameters of Glioblastoma

Abstract

Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. GBM-expansion depends on a dense vascular network and, coherently, GBMs are highly angiogenic. However, new intratumoral blood vessels are often aberrant with consequences for blood-flow and vascular barrier function. Hence, the delivery of chemotherapeutics into GBM can be compromised. Furthermore, leaky vessels support edema-formation, which can result in severe neurological deficits. The secreted signaling peptide Apelin (APLN) plays an important role in the formation of GBM blood vessels. Both APLN and the Apelin receptor (APLNR) are upregulated in GBM cells and control tumor cell invasiveness. Here we summarize the current evidence on the role of APLN/APLNR signaling during brain tumor pathology. We show that targeting APLN/APLNR can induce anti-angiogenic effects in GBM and simultaneously blunt GBM cell infiltration. In addition, we discuss how manipulation of APLN/APLNR signaling in GBM leads to the normalization of tumor vessels and thereby supports chemotherapy, reduces edema, and improves anti-tumorigenic immune reactions. Hence, therapeutic targeting of APLN/APLNR signaling offers an interesting option to address different pathological hallmarks of GBM.

Construction of an immune‐related prognostic model and potential drugs screening for esophageal cancer based on bioinformatics analyses and network pharmacology

“…For instance, previous studies have demonstrated a high expression of lncRNA ELFN1‐AS1 in pancreatic cancer cell lines and tissues, as well as a notable increase in cancer cell apoptosis and growth arrest via the gene knockdown of ELFN1‐AS1 29 . In glioblastoma cells, upregulation of both the APLN and the Apelin receptor ( APLNR ) allow control over the invasiveness of tumor cells take place 30 . Cancer cells fail to survive through the ubiquitination and destabilization of YAPI by certain protective genes, such as STUB1 and CTF1 , specifically the E3 ubiquitin ligase STUB1 31 .…”

“… 29 In glioblastoma cells, upregulation of both the APLN and the Apelin receptor ( APLNR ) allow control over the invasiveness of tumor cells take place. 30 Cancer cells fail to survive through the ubiquitination and destabilization of YAPI by certain protective genes, such as STUB1 and CTF1 , specifically the E3 ubiquitin ligase STUB1 . 31 Cardiotrophin‐1 ( CTF1 ) is a type of interleukin‐6 that has well‐established protective and hypertrophic actions towards cardiac myocytes, 32 but the connection between CTF1 and cancer is still not well‐explored.…”

Predicting feature genes correlated with immune infiltration in patients with abdominal aortic aneurysm based on machine learning algorithms

“…A ligand-activated helix-loop-helix transcription factor known as AHR -encoded proteins is implicated in the modulation of physiological reactions to planar aromatic hydrocarbons 35 , 36 . APLNR encodes a member of the gene family for G protein-coupled receptors, which, although linked to the angiotensin receptor, is actually an apelin receptor that inhibits adenylate cyclase activity and reverses the stress effects of angiotensin II (Ang II) by causing a hypertensive response 37 , 38 . ITGA10 encodes an integrin alpha chain and is highly expressed in chondrocytes.…”

Prognostic Estimation Model for Oligodendroglioma: An mRNA-Sequence Data-Based Analysis

“…Previous studies have shown that LOXL2, a member of the lysyl oxidase (LOX) family, not only promotes glioma cell proliferation, migration, and invasion and induces the epithelial-to-mesenchymal transition (EMT) process but also reduces the sensitivity of glioma cells to temozolomide (TMZ) [26] . APLN is activated by VEGF signalling and hypoxia-responsive elements in the APLN promoter, stimulates angiogenic sprouting, and plays a necessary and su cient role in tumour angiogenesis [27] . TROAP activates the Wnt/β-Catenin pathway and upregulates the expression of its downstream targets to play a tumour-promoting role [28] .…”