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Tony Hunter

 

Tony Hunter

Tony Hunter

Professor and American Cancer Society Professor
Molecular and Cell Biology Laboratory

"The goal of our group is to elucidate signal transduction mechanisms utilizing protein phosphorylation/ dephosphorylation, ubiquitination, and sumoylation and to investigate how these processes regulate cell proliferation, growth control, and the cell cycle. Ultimately, we want to use this information to uncover how dysregulation of such posttranslational modifications is involved in cancer."

Because of improved screening programs, most breast tumors are discovered at an early stage, when they are still small and confined. These tumors are known as DCIS (ductal carcinoma in situ), and the standard treatment consists of lumpectomy, the surgical removal of the tumor and surrounding tissue. Approximately 16 percent of DCIS patients treated with lumpectomy alone develop recurrent breast cancer growth within five years of treatment. One of the questions oncologists and patients face is whether they should add gamma radiation after surgery to catch straying tumor cells and reduce the risk of recurrent breast cancer. Better diagnostic methods that could predict whether the disease is likely to recur would aid in making this critical decision.

This need led Hunter and his team to wonder whether early-stage breast cancer that has not yet invaded the surrounding tissues might already contain highly motile cells, bringing the tumor one step closer to metastasis. For their study, they embedded human cells isolated from breast tissue in a three-dimensional matrix that mimics their natural surroundings. These cells spontaneously develop into so-called acini, hollow structures resembling tiny milk ducts. Then they turned on the ERK MAP kinase pathway, a signaling cascade frequently activated during the development of tumors, and watched in real time as breast cancer cells learned how to "walk." They quickly realized that there was a significant cell movement: Within 24 hours, a large number of these spheres had lost their organization, and the cells started to dance around.

While dangerously invasive cells can squeeze through the basement membrane and make a run for the surrounding tissue, the motile cells still could not escape the confines of the ERK-activated acini. But the acquisition of motility prior to invasion presumably lowers the barrier for future invasive growth. If a DCIS contains these highly motile cells, the patient may have an increased risk for recurrent growth, and adding radiation treatment regardless of tumor size may be prudent. In a next step, the researchers hope to identify molecular markers for breast cancer cell motility that will help oncologists diagnose patients who are at higher risk of metastasis.

Lab Photo

Left to right:
Back/standing: Tennaz Hasnat, Hidenori Matsuzaki, Zhongsheng You, Jeremy Copp, Jackson Crane, Justin Zimmerman, Gray Pearson, Zhiyong Wang, John Brognard, You-Wei Zhang, Paul Cheng, Andrea Carrano, Wei Zhu Front/seated: Jill Meisenhelder, Tony Hunter, Aaron Aslanian, Huaiyu Sun, Liz Baun, Beth Baber, Hui Ma

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Tony Hunter

Faculty

Tony Hunter

Tony Hunter

Professor and American Cancer Society Professor
Molecular and Cell Biology Laboratory

Tony Hunter, a professor in the Molecular and Cell Biology Laboratory and director of the Salk Institute Cancer Center, studies how cells regulate their growth and division, and how mutations in genes that regulate growth lead to cancer. His lab has made significant contributions in the area of signal transduction, how signals that stimulate or rein in growth are routed within a cell.

In 1979, his lab discovered that phosphate can be attached to tyrosine residues in proteins. This seminal discovery opened the door to the study of tyrosine kinases and their role in signal transduction, and in cell growth and development, as well as to their role in cancer and other human diseases. This knowledge already has resulted in a new approach to cancer treatment.

His current efforts are aimed at elucidating how protein phosphorylation, ubiquitination, and SUMOylation events are used to regulate cell proliferation and growth control, and cell cycle checkpoint activation in response to DNA damage. His recent work has highlighted the importance of crosstalk and feedback loops in the PI-3 kinase-Akt-mTOR cell growth pathway, has elucidated mechanisms of activation of the ATM protein kinase in response to double strand DNA breaks, and has identified a role for the ERK MAP kinase pathway in the motility of early breast carcinoma cells.

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