Recent advances in research on aspartate β-hydroxylase (ASPH) in pancreatic cancer: A brief update

Abstract

Pancreatic cancer (PC) is a highly aggressive tumor, often difficult to diagnose and treat. Aspartate β-hydroxylase (ASPH) is a type II transmembrane protein and the member of α-ketoglutarate-dependent dioxygenase family, found to be overexpressed in different cancer types, including PC. ASPH appears to be involved in the regulation of proliferation, invasion and metastasis of PC cells through multiple signaling pathways, suggesting its role as a tumor biomarker and therapeutic target. In this review, we briefly summarize the possible mechanisms of action of ASPH in PC and recent progress in the therapeutic approaches targeting ASPH.

Small-Molecule Chemical Knockdown of MuRF1 in Melanoma Bearing Mice Attenuates Tumor Cachexia Associated Myopathy

“…We selected EDL for proteomics because EDL weights are protected during Myomed-946 and -205 feeding ( Figure 2 D). A volcano plot comparison of EDL from healthy controls and BDF10 mice suggested specific alterations in EDL under melanoma-stress (see Figure S1 ), including Asph (a marker for tumor progression, maintenance, and also metastasis) [ 31 , 32 ], Pus7 (suggesting downregulation of protein synthesis [ 33 ]), Myl1 (myosin light chain 1; as recently also observed in human colon cancers and suggested as a marker for skeletal muscle cancer affection [ 34 ]), and Erc1 and Smdt1 (see Figure S2 ), both suggesting perturbed calcium-regulated cellular transport pathways: Erc1 belongs to the E, L, K, S protein rich (ELKS) family involved in Ca-dependent recruitment of vesicles to the synaptic cleft for exocytosis [ 35 ]; Smdt1 is a regulatory subunit of the mitochondrial uniporter that imports calcium into the mitochondrion [ 36 ]. Augmented Smdt1 may direct the mitochondrial Bax-pathway towards apoptosis [ 37 ].…”

Small-molecule active pharmaceutical ingredients of approved cancer therapeutics inhibit human aspartate/asparagine-β-hydroxylase

“… 2 , 3 Hypoxia is reported to regulate the expression levels of human AspH 4 , 5 and upregulated levels of AspH have been detected on the cell surface of invasive human cancers such as hepatocellular carcinoma, 6 , 7 breast cancer, 8 and pancreatic cancer. 9 AspH is reported to retain its catalytic activity on the cancer cell surface. 10 The upregulation of AspH and its translocalization from the endoplasmic reticulum (ER) membrane to the cell surface in cancer cells correlates with enhanced cell motility and metastatic spread resulting in a reduced lifespan of the affected patients.…”

Aspartate-β-Hydroxylase: A Promising Target to Limit the Local Invasiveness of Colorectal Cancer

“…ASPH is a highly conserved β-dioxygenase enzyme that is overexpressed in several cancer types [13]. ASPH plays important roles in tumor progression through the activation of the Notch signaling pathway, disruption of mitochondrial functions and inhibition of the antitumor activity of natural killer lymphocytes [4]. These pro-tumor activities could mediate the unfavorable prognostic effect of ASPH overexpression in renal, cervical, pancreatic, lung and thyroid cancer (protein atlas database: https://www.proteinatlas.org/ENSG00000198363-ASPH).…”

“…Notch, in turn, is involved in the stemness and drug resistance of colorectal cancer cells [1]. ASPH is upregulated in several malignant neoplasms (hepatocellular, pancreatic, lung and neural carcinomas) and correlates with a reduced survival rate [2][3][4][5][6]. In vitro, ASPH overexpression induces a malignant phenotype, characterized by increased motility and matrix invasion [7,8].…”