BAP1 promotes viability and migration of ECA109 cells through KLF5/CyclinD1/FGF‐BP1

Abstract

More than 40 000 patients worldwide die from esophageal cancer annually. The 5‐year survival rate of patients is only ~ 15–20%, and thus, there is an ongoing need to improve diagnosis and treatment of esophageal cancer. Breast cancer type 1 susceptibility protein (BRCA1)‐associated protein (BAP1) is a marker of poor prognosis in several cancers, including uveal melanoma, renal cell carcinoma, cholangiocarcinoma, non‐small cell lung cancer, and colorectal cancer. BAP1 mutations are early and rare events in esophageal carcinoma, but the involvement of BAP1 in progression of esophageal carcinoma is unclear. Here, we report that cell proliferation and migration were significantly enhanced in esophageal carcinoma ECA109 cells overexpressing BAP1, while they were diminished upon BAP1 knockdown. In addition, the expression of Krüppel‐like factor 5 (KLF5), CyclinD1, and FGF‐BP1 was increased by BAP1 overexpression and decreased by BAP1 knockdown. Our data suggest that BAP1 promotes cell proliferation and migration, and enhances the expression of KLF5 and its downstream genes, including CyclinD1 and FGF‐BP1, in the esophageal carcinoma cell line ECA109.

The roles and regulation of the KLF5 transcription factor in cancers

“…Consistently, crocin inhibited EMT, migration, and invasion of gastric cancer cells partially through increasing the expression of miR‐320, which targets KLF5 83 . Studies have found that overexpression of BAP1 in esophageal cancer cells upregulates the expression of KLF5 and its downstream genes FGF‐BP1 and Cyclin D1 , and promotes the proliferation and migration of ECA109 esophageal cancer cells 119 …”

“…and Cyclin D1, and promotes the proliferation and migration of ECA109 esophageal cancer cells. 119 In sharp contrast, KLF5 knockdown in A549 lung cancer cells induced EMT by downregulating the expression of E-cadherin and upregulating the expression of Vimentin protein. 120 Consistently, KLF5 is required to maintain epithelial characteristics and prevent EMT induction in epithelial cells by inducing the expression of miR-200.…”

“…42 In ECA109 cells, BAP1 can promote cell proliferation and migration by upregulating KLF5. 119 Additionally, KLF5, TP63, and SOX2 form a transcription complex to synergistically regulate the expression of target genes, including ALDH3A1, which is highly expressed in ESCC, and ALDH3A1 knockdown inhibits colony formation, cell viability and tumor growth in vivo. 37 This study also reported that the combination of the HDAC inhibitor romidepsin and the BET inhibitor ARV-771 can synergistically inhibit ESCC.…”

Genetic risk factors in melanoma etiopathogenesis and the role of genetic counseling: A concise review

“…The carriers of BAP1 gene mutations are also prone to developing clear cell renal cell carcinoma or mesothelioma [ 86 , 87 ]. More recent studies suggest that BAP1 mutations may indicate a poorer prognosis for these patients [ 88 ].…”

Erratum to: BAP1 promotes viability and migration of ECA109 cells through KLF5/CyclinD1/FGF‐BP1

“…In the paper by Wang et al. [ 1 ], the affiliation for Fengyun Wang was incorrect. The correct affiliation is given below:…”