MYB and HIF1α crosstalk drives hypoxia-induced transcriptional reprogramming and adaptive signaling alterations in pancreatic cancer

Authors

Shashi Anand, University of Mississippi Medical Center
Kunwar Somesh Vikramdeo, University of Mississippi Medical Center
Mohammad Aslam Khan, St. Jude Children's Research Hospital
Ajay Pratap Singh, University of Mississippi Medical Center

Author Type

faculty

Document Type

Article

Publication Title

Cancer Letters

Abstract

Pancreatic cancer is an aggressive malignancy, characterized by extensive desmoplasia and a hypoxic tumor microenvironment that contributes to therapy resistance. MYB, a proto-oncogene encoding a transcription factor, plays a crucial role in pancreatic tumor growth and metastasis. Recently, we also revealed a role of MYB in hypoxic survival of pancreatic cancer cells by promoting metabolic reprogramming through interaction with HIF1α, modulating its expression and binding to glycolytic gene promoters. In this study, we investigated how hypoxia influences the genome-wide occupancy of MYB using chromatin immunoprecipitation sequencing (ChIP-seq), and whether this effect is modulated by its interaction with HIF1α. In addition, we examined the genomic distribution of HIF1α in presence and absence of MYB and the impact of their crosstalk on the transcriptional output and associated signaling alterations by RNA sequencing (RNA-seq) and pathway analyses. Our findings show that hypoxia induces significant changes in the genomic distribution of MYB, which is partly dependent on HIF1α. We also demonstrate a significant impact of MYB on HIF1α genomic binding, identifying a subset of hypoxia-induced genes, co-regulated by MYB and HIF1α. These genes are involved in key metabolic and oncogenic signaling pathways critical for hypoxic adaptation. Together, these findings highlight the functional significance of reciprocal crosstalk between MYB and HIF1α, providing novel mechanistic insights into pancreatic cancer pathobiology.

DOI

https://doi.org/10.1016/j.canlet.2025.217916

Publication Date

7-16-2025

Comments

Funding

Recommended Citation

Anand, Shashi; Vikramdeo, Kunwar Somesh; Khan, Mohammad Aslam; and Singh, Ajay Pratap, "MYB and HIF1α crosstalk drives hypoxia-induced transcriptional reprogramming and adaptive signaling alterations in pancreatic cancer" (2025). Cell and Molecular Biology Publications. 8.
https://digitalcollections.umc.edu/cell-molecular-biology/8

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.