Ref-1 redox activity alters cancer cell metabolism in pancreatic cancer: exploiting this novel finding as a potential target
Abstract
Pancreatic cancer is a complex disease with a desmoplastic stroma, extreme hypoxia, and inherent resistance to therapy. Understanding the signaling and adaptive response of such an aggressive cancer is key to making advances in therapeutic efficacy. Redox factor-1 (Ref-1), a redox signaling protein, regulates the conversion of several transcription factors (TFs), including HIF-1α, STAT3 and NFκB from an oxidized to reduced state leading to enhancement of their DNA binding. In our previously published work, knockdown of Ref-1 under normoxia resulted in altered gene expression patterns on pathways including EIF2, protein kinase A, and mTOR. In this study, single cell RNA sequencing (scRNA-seq) and proteomics were used to explore the effects of Ref-1 on metabolic pathways under hypoxia.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 10, 2021
- Source ID
- 10.1186/s13046-021-02046-x
Entities
People
- Amber L. Mosely
- Bumsoo Han
- Chi Zhang
- Emily Hulsey
- Fenil Shah
- George E. Sandusky
- Hye-ran Moon
- Jing-Ruey Joanna Yeh
- Lee Armstrong
- Mark R. Kelley
- Melissa Fishel
- Mircea Ivan
- Nikkitha Umesh Ganesh
- Olivia Babb
- Silpa Gampala
- Xiaoyu Lu
Organizations
- Indiana Clinical and Translational Sciences Institute
- National Cancer Institute
- National Heart, Lung, and Blood Institute
- National Institute of General Medical Sciences
- National Institutes of Health