Li Wei, Chaowei Deng, Bo Zhang, Guanghui Wang, Yan Meng, Hao Qin
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引用次数: 0
Abstract
Specificity protein 4 transcription factor (SP4), a member of the Sp/Krüppel-like family (KLF), could bind to GT and GC box promoters, and plays an essential role in transcriptional activating. Despite SP4 having been detected to be highly expressed in a variety of human tumors, its biological effect and underlying molecular mechanism in esophageal squamous cell carcinoma (ESCC) remains unclear. Our research discovered that high SP4 expression is detected in primary ESCC specimens and cell lines and is strongly associated with the ESCC tumor grade and poor prognosis. In vitro, knockdown of SP4 suppressed cell proliferation and cell-cycle progression and promoted apoptosis, whereas overexpression of SP4 did the opposite. In vivo, inhibiting SP4 expression in ESCC cells suppresses tumor growth. Subsequently, we demonstrated that SP4 acts as the transcriptional upstream of PHF14, which binds to PHF14 promoter region, thus promoting PHF14 transcription. PHF14 was also significantly expressed in patient tissues and various ESCC cell lines and its expression promoted cell proliferation and inhibited apoptosis. Moreover, knockdown of SP4 inhibited the Wnt/β-catenin signaling pathway, whereas overexpression of PHF14 eliminated the effects of SP4 knockdown in ESCC cells. These results demonstrate that SP4 activates the Wnt/β-catenin signaling pathway by driving PHF14 transcription, thereby promoting ESCC progression, which indicates that SP4 might act as a prospective prognostic indicator or therapeutic target for patients with ESCC.
Implications: This study identified SP4/PH14 axis as a new mechanism to promote the progression of ESCC, which may serve as a novel therapeutic target for patients with ESCC.
期刊介绍:
Molecular Cancer Research publishes articles describing novel basic cancer research discoveries of broad interest to the field. Studies must be of demonstrated significance, and the journal prioritizes analyses performed at the molecular and cellular level that reveal novel mechanistic insight into pathways and processes linked to cancer risk, development, and/or progression. Areas of emphasis include all cancer-associated pathways (including cell-cycle regulation; cell death; chromatin regulation; DNA damage and repair; gene and RNA regulation; genomics; oncogenes and tumor suppressors; signal transduction; and tumor microenvironment), in addition to studies describing new molecular mechanisms and interactions that support cancer phenotypes. For full consideration, primary research submissions must provide significant novel insight into existing pathway functions or address new hypotheses associated with cancer-relevant biologic questions.