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SOX9 is a critical regulator of TSPAN8-mediated metastasis in pancreatic cancer
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SOX9 is a critical regulator of TSPAN8-mediated metastasis in pancreatic cancer
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Journal Article
SOX9 is a critical regulator of TSPAN8-mediated metastasis in pancreatic cancer
2021
Overview
Pancreatic ductal adenocarcinoma (PDAC) is the deadliest cancer mainly owing to its proclivity to early metastasis and the lack of effective targeted therapeutic drugs. Hence, understanding the molecular mechanisms underlying early invasion and metastasis by PDAC is imperative for improving patient outcomes. The present study identified that upregulation of TSPAN8 expression in PDAC facilitates metastasis in vivo and in vitro. We found SOX9 as a key transcriptional regulator of
TSPAN8
expression in response to EGF stimulation. SOX9 modulation was sufficient to positively regulate endogenous expression of TSPAN8, with concomitant in vitro phenotypic changes such as loss of cell–matrix adherence and increased invasion. Moreover, increased SOX9 and TSPAN8 levels were shown to correlate in human pancreatic cancer specimens and downregulated in vitro by EGFR tyrosine kinase inhibitors. High expression of SOX9 and TSPAN8 has been associated with tumor stage, poor prognosis and poor patient survival in PDAC. In conclusion, this study highlights the importance of the EGF-SOX9-TSPAN8 signaling cascade in the control of PDAC invasion and implies that TSPAN8 may be a promising novel therapeutic target for the treatment of PDAC.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 38/109
/ 38/77
/ 38/79
/ 692/53
/ 96/35
/ Cancer
/ Epidermal Growth Factor - metabolism
/ Epidermal Growth Factor - pharmacology
/ Gene Expression Regulation, Neoplastic - drug effects
/ Humans
/ Medicine
/ Oncology
/ Pancreatic Neoplasms - etiology
/ Pancreatic Neoplasms - metabolism
/ Pancreatic Neoplasms - mortality
/ Pancreatic Neoplasms - pathology
/ Patients
