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
Manipulating RKIP reverses the metastatic potential of breast cancer cells
Trang Huyen Lai, Mahmoud Ahmed, Jin Seok Hwang, Md Entaz Bahar, Trang Minh Pham, Jinsung Yang, Wanil Kim, Rizi Firman Maulidi, Dong-Kun Lee, Dong-Hee Kim, Hyun Joon Kim, Deok Ryong Kim
Frontiers in Oncology, vol. 13, 2023
Mahmoud Ahmed, Trang Huyen Lai, Deok Ryong Kim
Cancers, vol. 13(23), 2021
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
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
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