The PI3K-PTEN-AKT-TOR Signaling Pathway in Cancer, Metabolism, and Aging

The PI3K-PTEN-AKT-TOR Signaling Pathway in Cancer, Metabolism, and Aging

Friday, May 11, 2007

The New York Academy of Sciences

Presented By

 

Organizers: Pier Paolo Pandolfi, Memorial Sloan-Kettering Cancer Center; Domenico Accili, Columbia University

 

Program


8:15 - 8:45 AM
Registration & Continental Breakfast

8:45 - 9:00 AM
Introduction

Cancer

9:00 - 9:30 AM
Lewis Cantley, Harvard Medical School and Beth Israel Deaconess Medical Center

9:30 - 10:00 AM
Ramon Parsons, Columbia University

10:00 - 10:30 AM
Pier Paolo Pandolfi, Memorial Sloan-Kettering Cancer Center

10:30 - 11:00 AM
Break

Degeneration/Senescence

11:00 - 11:30 AM
Anne Brunet, Stanford School of Medicine

11:30 AM - 12:00 PM
David Sinclair, Harvard Medical School

12:00 - 1:30 PM
Luncheon

Diabetes/Metabolism

1:30 - 2:00 PM
Domenico Accili, Columbia University

2:00 - 2:30 PM
George Thomas, University of Cincinnati

2:30 - 3:00 PM
Barbara Kahn, Beth Israel Deaconess Medical Center

3:00 - 3:30 PM
Break

Therapy

3:30 - 4:00 PM
Peter Finan, Novartis Institutes for Biomedical Research

4:00 - 4:30 PM
David Sabatini, Whitehead Institute for Biomedical Research

4:30 - 5:00 PM
Charles Sawyers, Memorial Sloan-Kettering Cancer Center

5:00 - 5:15 PM
Closing Remarks

5:15 - 6:45 PM
Reception

 

Abstracts

 

PI3K and Cancer
Lewis C. Cantley
, PhD
Harvard Medical School and Beth Israel Deaconess Medical Center

Mutations in genes that control the phosphoinositide 3-kinase (PI3K) pathway are some of the most common events in human cancers. PI3K generates the lipid, phosphatidylinositol-3,4,5-trisphosphate (PIP3), that acts as a membrane bound second messenger to activate AKT/PKB family protein Ser/Thr kinases as well Tec family protein-Tyr kinases. PIP3 also regulates proteins that control Arf, Rac and Ras family GTP-binding proteins. This lipid is elevated in cancers, either due to loss of PTEN, the phosphatases that degrades it, or due to constitutive PI3K activity because of activating mutations in PIK3CA or an upstream activator of PI3K. The ultimate consequence of activating PI3K is to generate changes in signaling networks and gene expression patterns that promote cell growth, cell survival and cell movement. In order to elucidate the role of the PI3K pathway in cancer, we have generated mice in which genes for PI3K are deleted or activated in specific tissues. In addition, we have investigated the biochemical mechanisms by which PI3K becomes activated in human cancers. Our progress in these areas will be summarized.

Aberrant Signaling in Breast Cancer
Ramon Parsons
, MD, PhD
Columbia University

PTEN is mutated somatically in a small percentage of breast cancer cases; however, reduced PTEN protein occurs approximately ten times more frequently. At the same time PI3K is also often mutated in this disease. The relationships between PTEN and PI3K will be placed within the context of the heterogeneity of breast cancer. Examination of the impact of these two genes on cell signaling and tumor behavior will be discussed.

Pro-senescence Therapy for Cancer
Pier Paolo Pandolfi

Memorial Sloan-Kettering Cancer Center
Abstract to follow.

FOXO Transcription Factors in Aging
Ann Brunet
, PhD
Stanford School of Medicine

Longevity is regulated by modifications in single genes. The signaling pathway connecting insulin, Akt, and FOXO transcription factors provides the most compelling example for a conserved genetic pathway that regulates lifespan. FOXO transcription factors (FOXO) are directly phosphorylated in response to insulin/growth factor signaling by the protein kinase Akt, the