LITAF is a potential tumor suppressor in pancreatic cancer

Abstract

Early diagnosis of pancreatic cancer, one of the most deadly cancers with low survival rates, is difficult, and effective biomarkers are urgently needed. Lipopolysaccharide-induced tumor necrosis factor-α factor (LITAF) has been recently proposed as a potential tumor suppressor gene in several types of cancer. Here, we analyzed the biological function of LITAF in pancreatic cancer. The LITAF gene and protein levels were decreased in pancreatic tumor tissues compared with their paired adjacent non-cancerous tissues. In addition, patients with the lower LITAF protein expression had lower disease-free survival rates. The decreased LITAF expression correlated with LITAF promoter hypermethylation in pancreatic cancer cells and tissues. Moreover, promoter demethylation dose-dependently increased the LITAF transcription. Importantly, LITAF demethylation suppressed proliferation and cell cycle progression, and enhanced apoptosis of pancreatic cancer cells. Together, our results indicate that LITAF functions as a tumor suppressor gene in pancreatic cancer cells, and might serve as a novel biomarker for early diagnosis of pancreatic cancer.

Current Challenges and Opportunities in Treating Glioblastoma

“…Therefore, blocking the LITAF-STAT6(B) protein-protein interaction may be a viable treatment strategy. However, LITAF possesses a tumor-suppressing role in pancreatic cancer ( Zhou et al, 2018b ), and its expression can be induced by P53 ( Tang et al, 2007 ). LITAF knockdown promoted tumor malignancy and growth in nude mice injected subcutaneously with prostate cancer cells ( Zhou et al, 2011 ).…”

Involvement of the MicroRNA-1-LITAF Axis in Gastric Cancer Cell Growth and Invasion

“…LITAF is considered a tumor suppressor gene because its expression is regulated by p53 (5). Recent studies have shown that LITAF is frequently down-regulated in different cancers, including breast cancer, acute leukemia, lymphoma, prostate cancer, and pancreatic cancer (11)(12)(13)(20)(21)(22)(23). The possible mechanisms of the tumor-suppressive activity of LITAF (15) include promoting p53-and/or p72-mediated cell apoptosis following tumor growth restriction (24)(25)(26), promoting the ubiquitin-proteasome system in mediating the degradation of pro cancerous proteins (27), and acting as a downstream target of the tumor suppressor factor AMPK to stimulate TNFSF15 expression and then restrain angiogenesis, thereby inhibiting tumor growth (23).…”

“…Moreover, LITAF has been identified as a potential tumor suppressor gene because its expression can be induced by p53 (5). LITAF expression is significantly lower in tumor tissues, including those in breast cancer, pancreatic cancer, and acute leukemia (11)(12)(13) compared to the corresponding normal tissues. However, not all cancer cells exhibit low LITAF expression.…”

A novel epigenetic signature for predicting the prognosis of pancreatic ductal adenocarcinoma

“…Many reports suggested that aberrant DNA methylation is involved in the development and progression of pancreatic cancer. Tumor suppressor genes often show hypermethylation of the promoter, thereby suppressing its expression and contributing to the pathogenesis of PDAC [16,17]. Zhou et al [17] found that methylation frequencies of CpG sites within promoter of LITAF were signi cantly higher in PDAC tissues, and LITAF promoter hypermethylation was associated with low LITAF expression.…”