Zhijun Luo, MD, Ph.D

Action of AMPK on diabetes and cancer

One of our research interests is to elucidate the mechanism of AMPK regulation and function in insulin resistance, diabetes and cancer.   Solid evidence has indicated that increased levels of insulin/IGF1 and reactive oxidation species (ROS), which are associated with insulin resistance and type 2 diabetes, are risk factors for many types of cancer.  In these disorders, AMP-activated protein kinase (AMPK) is often found suppressed and activation of AMPK has been shown to correct or prevent these disorders and reduce the risk of cancer.  However, the underlying molecular mechanisms are not completely understood.  Thus, our research has been focusing on how AMP-activated protein kinase (AMPK) enhances insulin sensitivity, while it exerts a negative effect on tumor cell growth.  We are currently identifying molecular targets mediating the effects of AMPK. 

References.

1. Zang M, Gong J, Luo L, Zhou J Xiang X, Huang W, Huang Q, Luo X, Olbrot M, Peng Y, Chen C, Luo Z. Characterization of S338 phosphorylation in Raf-1 activation. J Biol Chem, 283:31429-37, 2008. PMC2581588

2. Chen Y, Wang R, Kun Z, Kwak Y-D, Liu Y, Ma T, Thompson RC, Zhao YB, Gasparini L, Luo Z, Xu H, Liao F-F. Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer’s amyloid peptides via upregulating BACE1 transcription. Proc Natl Acad Sci 106:3907-12, 2009. PMC2656178.

3. Zhou J, Huang W, Tao R, Ibaragi R, Lan L, Ido Y, Wu X, Alekseyev Y, Lendburg M, Hu G-F, Luo Z. Inactivation of AMPK alters gene expression and promotes growth of prostate cancer cells. Oncogene 28:1992-2002, 2009. PMC2679420.

4. Tao R, Gong J, Luo X, Guo W, Wen R, Luo Z. AMPK exerts dual regulatory effects on the PI3K pathway. J Mol Signal. 5:1-9, 2010, PMC 2854547.
Luo Z, Zang M, Guo W. AMP-activated protein kinase - metabolic tumor suppressor: control of metabolism and cell growth. Future Oncology 6:457-70, 2010, PMC 2854547.

5. Zhou J, Yang Z, Tsuji T, Gong J, Chen CY, Li W, Amar S, Luo Z. LITAF and TNFSF15, two downstream targets of AMPK, exert inhibitory effects on tumor growth. Oncogene. 30: 1892-900.2011, PMCID: PMC3431012

6. Luo L, Huang W, Tao R, Hu N, Xiao ZX, Luo Z. ATM and LKB1 dependent activation of AMPK sensitizes cancer cells to etoposide-induced apoptosis. Cancer Lett. 328:114-9, 2013. PMCID: PMC3521637.

 

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