TWIST1 correlates with Notch signaling pathway to develop esophageal squamous cell carcinoma
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TWIST1 correlates with Notch signaling pathway to develop esophageal squamous cell carcinoma Yasaman Fahim1 · Mozhgan Yousefi2 · Mohammad Hossein Izadpanah1 · Mohammad Mahdi Forghanifard2 Received: 16 June 2020 / Accepted: 17 July 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Notch signaling pathway mediates different biological processes including stem cell self-renewal, progenitor cell fate decision, and terminal differentiation. TWIST1 plays a key role in tumor development and metastasis through inducing epithelialmesenchymal transition (EMT). Expression of the core transcriptional complex of Notch pathway and its target genes, as well as TWIST1 overexpression, are closely related to the aggressive clinicopathological variables of esophageal squamous cell carcinoma (ESCC). Here we aimed to functionally elucidate probable crosstalk between TWIST1 and Notch pathway in ESCCs. Correlation between TWIST1 and Notch target genes was analyzed in 50 ESCCs and corresponding normal tissues. Using retroviral system, enforced expression of TWIST1 was established in ESCC line KYSE-30 cells and expression of Notch signaling genes was assessed. Significant correlation between TWIST1 and HEY1/HEY2 expression was found in different pathological variable of ESCC poor prognosis. Induced expression of TWIST1 in KYSE-30 cells caused a noteworthy increase of Notch pathway genes expression revealing regulatory role of TWIST1 on Notch signaling genes in the cells. Based on existed correlations between expression of TWIST1 and Notch pathway genes in different pathological features of ESCC patients, as well as KYSE-30 cell line, we may extrapolate that TWIST1 is involved in aggressiveness of the disease through regulation of Notch signaling genes. To the best of knowledge, this is the first report describing the impact of TWIST1 on Notch cascade genes in ESCC. Keywords TWIST1 · Notch signaling · ESCC · Poor prognosis
Introduction Esophageal squamous cell carcinoma (ESCC), as a dominant histological type of esophageal malignancies, is one of the most common diseases in the “Asian esophageal cancer belt” [1], with a 5-year survival rate as low as 15–25% [2]. Surgical resection, as a current therapeutic modality, is usually not an option for the ESCC patients when the disease is diagnosed in either advanced stages or metastatic states. Yasaman Fahim and Mozhgan Yousefi have contributed equally in this study. * Mohammad Mahdi Forghanifard [email protected]; [email protected] 1
Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Department of Biology, Damghan Branch, Islamic Azad University, Cheshmeh‑Ali Boulevard, Sa’dei Square, Damghan, Iran
2
Accordingly, a more effective targeted therapy is required to increase ESCC patients’ survival [3]. TWIST1 is a highly conserved basic helix–loop–helix (bHLH) transcription factor that recognizes and binds to a specific DNA sequence called E-box (CANNTG) [4]. Increasing evidences shown that TWIST1 plays a
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