The Role of CCN1 in Esophageal Adenocarcinoma: What We Have Learned From the Lab

Abstract

Background: Esophageal cancer is one of the most common and deadliest cancers in the world, particularly esophageal adenocarcinoma. There has never been a special drug to treat it. Purpose: This article summarizes the work that we have done in our laboratory about the role of CCN1 in esophageal cancer and gives a new perspective of CCN1 biology. Research Design: This is a review article. Study Sample: The work was done using validated cell lines and fixed human tissue slides. Data Collection and Analysis: This is a review article, therefore, no data collection or analysis was involved. Results: CCN1 is a matricellular protein supporting adhesion, migration, and survival in normal cells, but in the esophageal cancer cells, it induces TRAIL-mediated apoptosis. CCN1 promotes TRAIL and its death receptor expression but downregulates the decoy receptors and survivin in a p53-dependant manner. It was thought that CCN1 relies on TNF to induce apoptosis, but our study found that these two molecules antagonize each other. CCN1 promotes TNFR1 cleavage and uses the soluble product to block TNF signaling, while TNF upregulates PGLYRP1 to overcome this obstacle because PGLYRP1 is a secreted protein that competes with TNF for TNFR1 binding. As a result, when CCN1 and TNF are present together in the vicinity of esophageal tumors, they cancel each other out. Conclusions: Based on our laboratory study, CCN1 has much potential to be a candidate for the treatment of esophageal cancer.

Expression of Shh, Gli1, and Cyr61 in Gastric Cancer Predicts Overall Survival of Patients: A Retrospective Study

“…Studies have also shown that Cyr61 may activate Wnt, Shh, NF-κB, and COX2 signaling pathways in tumor cells. 24 - 26 Our study found that the expression of Cyr61 is closely related to Shh, indicating that these two proteins may promote each other in the progression of GC. Multivariate Cox proportional hazards regression analysis showed that patient age, Shh, Gli1, Cyr61 expression, TNM stage, and tumor differentiation were independent prognostic factors for OS in patients with GC.…”

Introductory Chapter: Do We Really Know GERD?

“…The reduction of acid secretion is simply not enough to stop GERD completely. Increasing evidence suggests that acid reflux may contribute to esophageal erosion but does not lead to malignancy; it is the bile reflux that induces the development of Barrett's esophagus and adenocarcinoma [26][27][28][29][30][31].…”

CCN proteins: opportunities for clinical studies—a personal perspective

“…Progress has been made for esophageal cancer (EAC) where the evidence suggests that CCN1 can override the inflammatory tumor progression factor TNFα to induce TRAIL and CCN1 leading to apoptosis (Chang et al 2022). Ackar et al (2021) found CCN1 as a circulating biomarker in plasma for the detection of lung cancer.…”