The catalytically defective receptor protein tyrosine kinase EphA10 promotes tumorigenesis in pancreatic cancer cells

Abstract

EphA10 (erythropoietin‐producing hepatocellular carcinoma receptor A10) is a catalytically defective receptor protein tyrosine kinase in the ephrin receptor family. Although EphA10 is involved in the malignancy of some types of cancer, its role as an oncogene has not been extensively studied. Here, we investigated the influence of EphA10 on the tumorigenic potential of pancreatic cancer cells. Analysis of expression profiles from The Cancer Genome Atlas confirmed that EphA10 was elevated and higher in tumor tissues than in normal tissues in some cancer types, including pancreatic cancer. EphA10 silencing reduced the proliferation, migration, and adhesion of MIA PaCa‐2 and AsPC‐1 pancreatic cancer cells. These effects were reversed by overexpression of EphA10 in MIA PaCa‐2 cells. Importantly, overexpression and silencing of EphA10 respectively increased and decreased the weight, volume, and number of Ki‐67‐positive proliferating cells in MIA PaCa‐2 xenograft tumors. Further, EphA10 expression was positively correlated with invasion and gelatin degradation in MIA PaCa‐2 cells. Moreover, overexpression of EphA10 enhanced the expression and secretion of MMP‐9 in MIA PaCa‐2 cells and increased the expression of MMP‐9 and the vascular density in xenograft tumors. Finally, expression of EphA10 increased the phosphorylation of ERK, JNK, AKT, FAK, and NF‐κB, which are important for cell proliferation, survival, adhesion, migration, and invasion. Therefore, we suggest that EphA10 plays a pivotal role in the tumorigenesis of pancreatic epithelial cells and is a novel therapeutic target for pancreatic cancer.

Effects of Tenascin C on the Integrity of Extracellular Matrix and Skin Aging

“…Total RNA isolation, cDNA synthesis, and RT-PCR analysis were performed as previously described with minor modifications [ 51 , 52 ]. Total RNA was isolated from the mouse skin tissues and fibroblasts using TRIzol (Invitrogen).…”

PTK7, a Catalytically Inactive Receptor Tyrosine Kinase, Increases Oncogenic Phenotypes in Xenograft Tumors of Esophageal Squamous Cell Carcinoma KYSE-30 Cells

“…Mice were sacrificed 6 weeks after cell injection. The xenograft tumors were recovered to measure tumor weight, fixed in formalin, and were paraffin embedded for histological and immunohistochemical analyses [60].…”

Ephrin receptor A10 monoclonal antibodies and the derived chimeric antigen receptor T cells exert an antitumor response in mouse models of triple-negative breast cancer

“…In addition to its role in promoting TNBC, EphA10 upregulation has been shown to promote tumorigenesis in other types of cancer, such as pancreatic (19) and prostate (20) cancers. Indeed, results from The Cancer Genome Atlas (TCGA) RNA-sequencing database showed that the EphA10 mRNA level was significantly higher in tumor tissues than in normal controls in all breast invasive carcinoma (BRCA) subtypes including basal-like TNBC (Supplementary Fig.…”

“…Ephrin receptor A10 (EphA10), a member of the Eph subfamily, is not expressed in normal human adult tissue except in the testis ( 16 , 17 ). In contrast, EphA10 expression is common in malignant cells across histology of various tumors and has been associated with poor prognosis in patients with breast, prostate, and gallbladder cancers ( 17 , 18 , 19 , 20 , 21 ). In human breast cancer specimens, expression of EphA10, as assessed by IHC, has been significantly correlated with lymph node metastasis and higher tumor stage ( 22 ).…”