Presentation Title

Growth Factor Signaling in Response to Extracellular Matrix Remodeling with Hyaluronidase Increases Glucose Metabolism

Faculty Mentor

Dr. Heather Christofk

Start Date

18-11-2017 9:15 AM

End Date

18-11-2017 9:30 AM

Location

9-255

Session

Bio Sciences 1

Type of Presentation

Oral Talk

Subject Area

biological_agricultural_sciences

Abstract

Hyaluronan is an important carbohydrate component in the extracellular matrix (ECM) whose dynamic secretion and digestion are involved in a variety of tissue reorganization processes. Treatment of cells with hyaluronidase (HAase), an enzyme that digests the polymer, promotes increased glycolysis, though the pathway by which this occurs remains unknown. Upregulation of glycolysis has been shown to be dependent on the induction of the mRNA decay factor TTP, which targets the TXNIP transcript - which encodes a negative regulator of the glucose transporter GLUT1 - for degradation. The aim of this study was to identify the signaling events triggered by HAase treatment that induces TTP and the subsequent decrease in TXNIP. We found a variety of growth factor receptors exhibit increased activity upon HAase treatment across different cell lines. Inhibition of these receptors demonstrated a rescue in the change of TTP and TXNIP levels when treated with HAase, further suggesting their role in the TTP-TXNIP-GLUT1 axis. Here, we propose that the disengagement of the full-length hyaluronan polymer from the cell surface triggers growth factor receptor signaling that alters a central regulatory node of glucose metabolism. These findings further develop our appreciation of the ECM as a novel point of cell-extrinsic metabolic regulation.

Summary of research results to be presented

1. HAase treatment leads to the activation of various RTKs across different cell lines.

2. Inhibition of RTKs rescues changes in TTP and TXNIP levels when co-treated with HAase suggesting their role upstream of the TTP-TXNIP-GLUT1 axis.

3. We propose the disengagement of the full length hyaluronan polymer from RTKs upon HAase treatment initiates growth factor signaling leading to the increased expression of TTP, degradation of TXNIP mRNA, and increased plasma membrane GLUT1 levels.

4. Our findings help further develop our understanding of how the ECM acts as a novel point cell-extrinsic metabolic regulation and our understanding of the heterogeneity of cells in tissues.

5. Beyond describing the effects matrix remodeling has on malignancies, our findings have broader implications in understanding the role of HAase in the context of wound healing and early-embryonic development.

This document is currently not available here.

Share

COinS
 
Nov 18th, 9:15 AM Nov 18th, 9:30 AM

Growth Factor Signaling in Response to Extracellular Matrix Remodeling with Hyaluronidase Increases Glucose Metabolism

9-255

Hyaluronan is an important carbohydrate component in the extracellular matrix (ECM) whose dynamic secretion and digestion are involved in a variety of tissue reorganization processes. Treatment of cells with hyaluronidase (HAase), an enzyme that digests the polymer, promotes increased glycolysis, though the pathway by which this occurs remains unknown. Upregulation of glycolysis has been shown to be dependent on the induction of the mRNA decay factor TTP, which targets the TXNIP transcript - which encodes a negative regulator of the glucose transporter GLUT1 - for degradation. The aim of this study was to identify the signaling events triggered by HAase treatment that induces TTP and the subsequent decrease in TXNIP. We found a variety of growth factor receptors exhibit increased activity upon HAase treatment across different cell lines. Inhibition of these receptors demonstrated a rescue in the change of TTP and TXNIP levels when treated with HAase, further suggesting their role in the TTP-TXNIP-GLUT1 axis. Here, we propose that the disengagement of the full-length hyaluronan polymer from the cell surface triggers growth factor receptor signaling that alters a central regulatory node of glucose metabolism. These findings further develop our appreciation of the ECM as a novel point of cell-extrinsic metabolic regulation.