Kenneth V. Honn
Kenneth V. Honn, Ph.D.
431 Chemistry Building
Detroit, MI 48202
- The role played by eicosanoids, bioactive lipids, in cancer cell motility and invasion, an area that we pioneered.
- Adhesion receptors, in particular integrins and their role in metastasis.
There is a direct correlation between the stage and grade of prostate cancer and the ratio of 12-lipoxygenase to 15-lipoxygenase-2 enzymes. Over expression of 12-lipoxygenase (12-LOX), and the metabolic product of its arachidonic acid substrate, 12(S)-HETE, shields tumor cells from apoptotic programs initiated, for example, by radiation therapy. This leads to selection and survival of 'radioresistant' cancer cells that contribute to morbidity and mortality. 12-LOX also imparts tumor resistance to anti-angiogenic agents. Inherent in the tumor cell 'survival' program is 12-LOX-mediated up-regulation of integrins, in particular αvβ3 and αvβ5, stimulation of endothelial cell migration, and enhanced angiogenic responses through the release of vascular endothelial growth factor. Activation of 12-LOX occurs in response to a variety of cytokines. Its activity is modulated by mobilization within the cell and subsequent physical interaction with the cytoplasmic tail of the β4 integrin, an integrin known to play a major role in the invasive process of numerous cancers. To date we have determined that 12-LOX and β4 integrin collaborate in carcinoma invasion in vitro and tumor progression in animal models by means of a complex cross talk of phosphorylation, protein trafficking, and transcriptional activation.
Advanced imaging technology is the bridge between biochemical data and mechanistic data generated from animal studies. The ability to track proteins at high resolution in real time under carefully controlled conditions is essential for defining precise contributions of temporal and physical redistribution of protein complexes within a cell, as well as cell movement and differentiation within 3D cultures and within tissues of live animals. Furthermore, the ability to perform such studies with reduced photo-damaging/cytotoxicity and on thicker specimens would allow for smaller specimen numbers and yield more clinically relevant data especially when imaging processes such as neovascularization in situ.
Lövey J, Nie D, Tóvári J, Kenessey I, Kandouz M, Tímár J, Kásler M, Honn KV. [Selective 12-lipoxygenase inhibition potentiates the effect of radiation on human prostate cancer cells in vitro and in vivo]. Magy Onkol. 2014;58:211-8.
Maddipati KR, Romero R, Chaiworapongsa T, Zhou SL, Xu Z, Tarca AL, Kusanovic JP, Munoz H, Honn KV. Eicosanomic profiling reveals dominance of the epoxygenase pathway in human amniotic fluid at term in spontaneous labor. FASEB J. 2014:fj.14-254383. [Epub ahead of print]
Menter DG, Tucker SC, Kopetz S, Sood AK, Crissman JD, Honn KV. Platelets and cancer: a casual or causal relationship: revisited. Cancer Metastasis Rev. 2014;33:231-69.
Kast RE, Tucker SC, Killian K, Trexler M, Honn KV, Auner GW. Emerging technology: applications of Raman spectroscopy for prostate cancer. Cancer Metastasis Rev. 2014;33:673-93.
Zhang W, Zhao J, Lee JF, Gartung A, Jawadi H, Lambiv WL, Honn KV, Lee MJ. ETS-1-mediated transcriptional up-regulation of CD44 is required for sphingosine-1-phosphate receptor subtype 3-stimulated chemotaxis. J Biol Chem. 2013;288:32126-37.
Zhang W, An J, Jawadi H, Siow DL, Lee JF, Zhao J, Gartung A, Maddipati KR, Honn KV, Wattenberg BW, Lee MJ. Sphingosine-1-phosphate receptor-2 mediated NFκB activation contributes to tumor necrosis factor-α induced VCAM-1 and ICAM-1 expression in endothelial cells. Prostaglandins Other Lipid Mediat. 2013 Jun 11.
Dilly AK, Ekambaram P, Guo Y, Cai Y, Tucker SC, Fridman R, Kandouz M, Honn KV. Platelet-type 12-lipoxygenase induces MMP9 expression and cellular invasion via activation of PI3K/Akt/NF-κB. Int J Cancer. 2013;133:1784-91.
Tucker SC, Honn KV. Emerging targets in lipid-based therapy. Biochem Pharmacol. 2013;85:673-88.
Education and Training:
BS in Biological Sciences (1967): Wayne State University, Detroit, Michigan
MS in Biological Sciences (1968): Wayne State University, Detroit, Michigan
PhD in Endocrinology (1977): Wayne State University, Detroit, Michigan