JCSMR School Seminar Series: Deregulation of cancer energy metabolism during tumorigenesis

Dr Mong-Hong Lee, Professor in the Department of Molecular and Cellular Oncology of The University of Texas MD Anderson Cancer Center (UTMDACC) and faculty member at The University of Texas Graduate School of Biomedical Sciences, Houston, US.

Tumorigenesis is characterized by 10 hallmarks. Among these, deregulation of cellular energetics involves tumor cells “rewiring” their metabolic pathways to support rapid proliferation, continuous growth, metastasis, survival, and resistance to therapies. However, the mechanism behind deregulation of cancer cellular energetics remains elusive. The expression of 14-3-3σ is frequently lost in tumors of epithelial origin, including most breast cancers. Our analysis indicated that deficiency of 14-3-3σ expression in breast cancers correlated with patients’ poor survival. Results of our studies in breast cancer cell lines, murine xenograft tumors, and human breast tumors revealed previously unknown activities of 14-3-3σ in suppressing major cancer hallmarks, especially deregulation of cellular energetics. We show that 14-3-3σ inhibits cancer metabolic reprogramming by promoting Myc degradation, thereby reversing the oncogenic changes in cellular bioenergetics of tumors. 14-3-3σ could be considered as a potential target for future development of targeted anticancer therapies.

Dr Lee received his PhD degree in Molecular, Cellular, and Developmental Biology from the University of Pittsburgh, where he received the Stanton C Crawford Award for teaching excellence and Andrew Mellon fellowship. He then went on to complete a postdoctoral fellowship while serving as a research associate at Howard Hughes Medical Institute and Memorial Sloan-Kettering Cancer Center. After completing his postdoctoral fellowship, Dr Lee came to UTMDACC in 1997 as a faculty member. Dr Lee’s early work on slow growing mycobacteria (PNAS 1991; Nature 1991) and later research work on characterizing the roles of Cdk inhibitors (Cell 1994; G&D1995) in human cancer formation have shaped his aspiration to exploit cell cycle regulation in cancer therapy. Dr Lee has set up research projects focusing on: 1) roles of two CKI molecules that he was involved in cloning (p27, 14-3-3σ) in tumorigenesis 2) COP9 signalosomemediated cancer signaling regulation, 3) investigating the impact of hypoxia and Pim1 kinase in cancer drug resistance, 4) employing Aurora B kinase inhibitor for cancer therapy, and 5) investigating the impact of obesity and diabetic conditions on the tumor cancer growth. Over the years, Dr Lee has been engaged in the important discoveries of cell cycle regulation and tumor suppression. Dr Lee was involved in the discoveries of the cyclin–dependent kinase inhibitor p27kip1 (Cell 1994), p57kip2 (G&D 1995; G&D 1997). At UTMDACC, he and his colleagues demonstrated the first evidence for the functional activity of HER2 in enhancing ubiquitin-mediated degradation of p27 (JBC 2000) and p21 (NCB 2000), discovered the regulation of MDM2-p53 by 14-3-3σ tumor suppressor (MCB 2003; Oncogene 2007), characterized the role of 14-3-3σ in Akt and p27 regulation (Cancer Research 2006; Oncogene 2006), elucidated the role of Pim1 kinase in hypoxia induced chemoresistance (Oncogene 2009; Am J Pathol 2009), developed and characterized knockout mice for Cop9 signalosome subunit 6 gene and demonstrated its role in controlling Mdm2-p53 axis in DNA damage response and cancer formation (JCI 2011), identified COP1 as an E3 ligase for 14-3-3σ (Oncogene 2011) and characterized association between p53, Aurora B, and Aurora A during mitosis (PNAS 2012; Cell Cycle 2012). Recently, in close collaboration with his colleagues, they organize a new research project to determine the signal regulation of obesity/diabetes in affecting the clinical outcome on various types of cancer and propose a clinical trial for obese breast cancer patients. Dr Lee also has served in more than 140 PhD student committees including examination, advisory, and supervisory committees. More than 160 trainees including summer students have gained research experience in his lab. Dr Lee received outstanding educator award at UTMDACC (2003), was awarded the John P McGovern Outstanding Teaching Award (2009) selected among the approximately 570 UTMDACC and GSBS members of faculty, and was named as an educator of the month at UTMDACC (2010). He was recently awarded “US Faculty Scholar Award” by Vietnam Education Foundation of US government (2013).

Dr Lee has been an ad hoc reviewer for more than 27 biomedical/cancer journals, including PNAS, Cancer Research, JCI, Oncogene, and Nature Review of Cancer. Dr Lee has been the principal investigator or a co-principal investigator for nine funded research projects from NCI, DOD, and Susan G Komen race for cure.  He also has been a grant reviewer for several funding agencies. He maintains social media including Cancer Hallmark Tribune, Cancer Hallmark twitter, facebook, and Weibo for sharing cancer research news with general and science communities. He has pioneered the launch of the Cancer Hallmark Journal, focusing on basic, clinical and epidemiological cancer research. He is the Editor-in-Chief. He would like to help establish a journal shared by the cancer research community with a hope to render objective, constructive, and decisive review for cancer researchers to publish their research endeavor.

Date & time

3–4pm 20 September 2013

Location

The Finkel Lecture Theatre, The John Curtin School of Medical Research, Building 131, Garran Road, ANU

Contacts

 Laura Vitler
 02 6125 2589

Updated:  24 October 2017/Responsible Officer:  Director, JCSMR/Page Contact:  Web Manager