Postdoc - Biomedicine

Transcriptional regulation of RKIP in cancer



This project is a collaboration with my colleague Trang Huyen Lai

Summary

Raf kinase inhibitory protein (RKIP), also known as a phosphatidylethanolamine-binding protein 1 (PEBP1), functions as a tumor suppressor and regulates several signaling pathways, including ERK and NF-κB. RKIP is severely downregulated in human malignant cancers, indicating a functional association with cancer metastasis and poor prognosis. In this project, we aim to decipher the regulatory circuits responsible for RKIP loss in different cancer cell models. We use a variety of public data analysis and experimental techniques. Identifying the role of the regulators broadens our understanding of metastasis and represents new targets for therapeutics. 
The following are key findings from the work. 
  • MTDH is a novel transcriptional co-factor that controls RKIP transcription, which is essential for breast cancer progression.
  • VEZF1 and ERCC6 simultaneously target RKIP and one or more of the autophagy genes in prostate cancer.
  • RKIP and its co-expressed autophagy genes are co-regulated by common transcription factors as part of the same functional unit in developing prostate cancer.
  • The metastasis suppressor RKIP is on the receiving end of two significant regulatory mechanisms. One involves RELA (transcription factor P65) and SNAI1, which were previously reported to inhibit PEBP1. The other involves the estrogen receptor (ESR1), which induces PEBP1 through the kinase NME1.
  • Pharmacologically manipulating RKIP reverses the metastatic potential of breast cancer cells.

Publications


Functional Linkage of RKIP to the Epithelial to Mesenchymal Transition and Autophagy during the Development of Prostate Cancer.


Mahmoud Ahmed, Trang Huyen Lai, Sahib Zada, Jin Seok Hwang, Trang Minh Pham, Miyong Yun, Deok Ryong Kim


Cancers, vol. 10(8), 2018 Jul 16


Anti-cancer effect of RKIP via modulating autophagy during metastasis


Mahmoud Ahmed, Deok Ryong KIm


Prognostic and Therapeutic Applications of RKIP in Cancer, Benjamin Bonavida, Stavroula Baritaki, chapter 15, 1st ed., vol. 1, Academic Press, 2020, pp. 277-293


Transcriptional Repression of Raf Kinase Inhibitory Protein Gene by Metadherin during Cancer Progression.


Trang Huyen Lai, Mahmoud Ahmed, Jin Seok Hwang, Sahib Zada, Trang Minh Pham, Omar Elashkar, Deok Ryong Kim


International Journal of Molecular Sciences, vol. 22(6), 2021 Feb 17


A functional network model of the metastasis suppressor RKIP and its regulators in breast cancer cells


Mahmoud Ahmed, Trang Huyen Lai, Deok Ryong Kim


Cancers, vol. 13(23), 2021

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