Decreased expression of Annexin A10 in gastric cancer and its overexpression in tumor cell growth suppression

Abstract

Abstract. Gastric carcinoma is the most common neoplasm in Southeast Asian populations and is the second leading cause of cancer death worldwide. Annexins are a family of cytosolic calcium and membrane binding proteins that have been implicated in a wide variety of cell functions. Recent studies have suggested that Annexin A10 (ANXA10), a member of the Annexin protein family, is down-regulated in specific types of cancer. However, the underlying molecular mechanisms of the dysregulation of ANXA10 remain to be elucidated. In the present study, to investigate the biological effects of ANXA10 on gastric carcinoma, aberrant expression of ANXA10 was evaluated by Western blot analysis, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC), in gastric cancer tissues and cell lines. Decreased expression of ANXA10 was observed in five selected gastric cancer tissues compared to the normal surrounding mucosa. In the cancer cell lines, seven out of nine selected gastric cancer cell lines had no detectable ANXA10 by RT-PCR. Among these, when an ANXA10 expressing plasmid was introduced into MKN-1 cells, cell growth was suppressed and apoptosis augmented. The results of this study demonstrated that ANXA10 was aberrantly regulated in gastric carcinoma and suggests that down-regulation of ANXA10 might be involved in gastric carcinogenesis. In addition, ANXA10 may play a role, as a tumor suppressor, in the development and progression of gastric cancer.

Frequent Alteration of Annexin A9 and A10 in HPV-Negative Head and Neck Squamous Cell Carcinomas: Correlation with the Histopathological Differentiation Grade

“…Several studies have identified ANXA10 as a tumor suppressor, diagnostic marker, potential therapeutic target, or prognostic factor in various malignancies, including bladder cancer, hepatocellular carcinoma, acute myeloid leukemia, gastric carcinoma, oral squamous cell carcinoma, pancreatobiliary adenocarcinoma, and urothelial carcinoma [33,34,35,36,37]. Studies have shown that ANXA10 was down-regulated in hepatocellular carcinoma and was associated with a poor prognosis [34,35].…”

“…Additional studies are ongoing to establish the pathogenic roles of these proteins in the progression of squamous cell carcinomas of the head and neck and especially, to determine whether their altered expression is a cause or consequence of the cancerous state. The association of ANXA9 with pathogenic prognosis in colorectal cancer [13] contrasts with a proposed tumor suppressor role for ANXA10 in gastric cancer [36]. The unique, calcium-independent actions of these two annexins may also contribute to a better understanding of their underlying mechanisms.…”

Characters of KRT80 and its roles in neoplasms diseases

“…In the study by Ishikawa, A. et al, KRT80 was suggested to be potentially associated with the ANXA10 regulatory pathway in GC, and ANXA10 knockdown was able to increase the proliferation 25,39 and invasiveness 40 of GC cell lines as well as their sensitivity to 5-FU. 41 GC has contributed to much of the research on KRT80 in cancer.…”

Role of annexin A family in tumorigenesis and chemoresistance of gastric cancer

“…A recent study from Japan reported that the loss of ANXA10 expression was detected in 61.2% of early GC patients and also significantly associated with poor OS [113]. ANXA10 may affect the development of GC by inhibiting the malignant phenotype [114]. When an ANXA10 overexpressing plasmid was introduced into MKN-1 GC cells, the cell growth was suppressed, and apoptosis was augmented [114].…”

“…ANXA10 may affect the development of GC by inhibiting the malignant phenotype [114]. When an ANXA10 overexpressing plasmid was introduced into MKN-1 GC cells, the cell growth was suppressed, and apoptosis was augmented [114]. In addition, ANXA10 was also involved in the induction of pancreatic duodenal homeobox 1(PDX1) expression in GC [112].…”