American Association for Cancer Research

Targeting Protein Quality Control for Cancer Therapy

Summary

The normal growth and proliferation of cells is orchestrated by a cascade of events that is initiated by binding of a stimulus to a receptor at the membrane. Once triggered, the receptor communicates to the rest of the cell via recruitment of a number of signaling molecules. In cancer, the alteration of growth or survival signals can ultimately cause the signaling circuits to go out of control. Abnormal changes in receptor levels generate more cell changes that lead to uncontrolled growth. Most cancer therapy takes advantage of this phenomenon. Current drugs bind to these growth receptors at the membrane. However, drug resistance can develop over time. Recently, Jacinto discovered that a protein complex, mTORC2, that is known for its function in activating the protein Akt has a crucial role in protein production and quality control. She found that mTORC2 also controls growth receptors such as epidermal growth factor receptor. Jacinto will examine this novel function of mTORC2 in regulating epidermal growth factor receptor expression and quality control. Drugs that can target mTORC2 would thereby “hit two (or more) birds with one stone.” Inhibiting mTORC2 in cancer would prevent cell survival and blocking the expression of epidermal growth factor receptor before it reaches the cell membrane, thereby preventing growth of cancer cells. Jacinto will use cell and mouse models to inhibit mTORC2 in breast cancer cells. This could have implications in a number of cancer types, and ultimately reveal new modes of therapy for breast cancer and other malignancies.

Investigator

Estela Jacinto, Ph.D., is assistant professor in the department of physiology and biophysics at the University of Medicine & Dentistry of New Jersey - Robert Wood Johnson Medical School.

Updated: April 4, 2011