PDGFRα and β play critical roles in mediating Foxq1-driven breast cancer stemness and chemoresistance

Fanyan Meng, Cecilia L. Speyer, Bin Zhang, Yongzhong Zhao, Wei Chen, David H. Gorski, Fred R. Miller, Guojun Wu

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Many epithelial-mesenchymal transition (EMT)-promoting transcription factors have been implicated in tumorigenesis and metastasis as well as chemoresistance of cancer. However, the underlying mechanisms mediating these processes are unclear. Here, we report that Foxq1, a forkhead box-containing transcription factor and EMT-inducing gene, promotes stemness traits and chemoresistance in mammary epithelial cells. Using an expression profiling assay, we identified Twist1, Zeb2, and PDGFRα and β as Foxq1 downstream targets. We further show that PDGFRα and β can be directly regulated by Foxq1 or indirectly regulated through the Foxq1/Twist1 axis. Knockdown of both PDGFRα and β results in more significant effects on reversing Foxq1-promoted oncogenesis in vitro and in vivo than knockdown of either PDGFRα or β alone. In addition, PDGFRβ is a more potent mediator of Foxq1-promoted stemness traits than PDGFRα. Finally, pharmacologic inhibition or gene silencing of PDGFRs sensitizes mammary epithelial cells to chemotherapeutic agents in vitro and in vivo. These findings collectively implicate PDGFRs as critical mediators of breast cancer oncogenesis and chemoresistance driven by Foxq1, with potential implications for developing novel therapeutic combinations to treat breast cancer.

Original languageEnglish
Pages (from-to)584-593
Number of pages10
JournalCancer Research
Volume75
Issue number3
DOIs
StatePublished - 1 Feb 2015
Externally publishedYes

Fingerprint

Dive into the research topics of 'PDGFRα and β play critical roles in mediating Foxq1-driven breast cancer stemness and chemoresistance'. Together they form a unique fingerprint.

Cite this