Nancy E. Hynes: “Memo is required for migration and metastasis”

Nancy E Hynes (1)

The last October 30th took place the extraordinary IDIBELL seminar “Targeting signaling pathways in breast cancer” by Nancy E. Hynes, researcher and leader of the Mechanisms of Cancer group at the Friedrich Miescher Institute for Biomedical Research, and hosted by Dr. Sara Kozma. Dr. Hynes talked about Memo, a novel enzyme related to metastasis in breast cancer.

“We prepared transcriptome analysis to study the pathways in breast cancer”, said Nancy E. Hynes, researcher at the Friedrich Miescher Institute for Research. In the development, the Ret receptor tyrosine kinase promotes migration, survival and differentiation of the nervous system. The inflammatory related genes upregulated by the Ret activation during endocrine therapy, increase the IL6 levels in response to endocrine therapy. The researchers found highest levels of IL6 in cells treated with fulvestrant. IL6 interacts with Ret loop and it also promotes migration. FAK kinase was activated about Ret and IL6. The FAK inhibition blocks IL6 and Ret induced signalling. IL6 in the CM is required for migration. IL6 mAb blocks migration of cells treated GDNF and fulvestrant. IL6 increases in response to endocrine agents.

Breast cancer models: testing the Ret role

“Does Ret have a role in vivo in tumour growth and metastasis? We used two models to answer this question. With J110 ER+/Ret+ metastasis cancer model we saw that AST487 reduces Ret and Akt activity. The J110 Ret – metastasis cancer model was very similar”, said the researcher. Ret inhibition lowers IL6 and Ret expression in tumours in vivo. P-FAK levels are lower in AST487 treated tumours. And blocking Ret kinase activity interferes with the Ret-IL6 loop and blocks FAK kinase, decreased Ret levels.

In vivo models, in ER+/Ret+ breast cancer model, Ret and ER cooperate to promote proliferation. For patients, Ret is overexpressed in a number of breast tumours: ER+ and other subgroups.

Memo and metastasis

The Mediator of ErbB2-driven Cell Mobility, as known as Memo, expression levels in human tumours decreases the invasion and the migration of MDA-MB231 breast tumour. Memo is required for lung cancer, but not for MDA-MB231 tumour.

Memo is related with metastasis and interacts with RhoA. It is also required for a rapid RhoA activation. Memo, that adopts a single domain structure, has an oxidoreductase activity and produces superoxide. “Memo is a novel, conserved redox enzyme that is required for migration in response to a wide range of ligands, and for metastasis. The enzymatic activity of Memo is required for migration”, concluded the researcher.

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