Insulin helps cells become invasive in breast cancer

The data reveals that IRS-2 expression sensitizes breast carcinoma cells.

Dr. Jose Mercado Matos,

During his five doctoral years, physician José Mercado Matos studied metastatic disease and insulin related to breast cancer and tried to understand how cancer cells leave their primary tumor and become metastatic.

Their research discovered that a protein – insulin receptor substrate 2, or IRS2 – contributes to the ability of cells to become invaders. In the future, he hopes to develop methods to address the region without disrupting its ability to regulate important metabolic functions.

“Insulin IRS2s serve as essential signaling intermediaries for the activation of phosphoinositol 3-kinase (PI3K) by both the insulin-like growth factor receptor 1 (IGF-1R) and its close relative, the insulin receptor. Although insulin IRS-1 and IRS-2 share significant homology, they regulate distinct cellular responses directed at these receptors and play divergent roles in the breast cancer“, he explains in his investigative work.

Treatment with drugs that stabilize or disrupt microtubules reveals that an intact microtubule cytoskeleton contributes to IRS-2-mediated activation of AKT but not to IRS-1 by IGF-1. Proximal IGF-1R signaling events, including IRS tyrosine phosphorylation and PI3K recruitment, are not inhibited by microtubule disruption, indicating that IRS-2 requires the microtubule cytoskeleton for activation. of the downstream effector.

IRS-2 colocalization with tubulin is enhanced by Taxol-mediated microtubule stabilization which, together with signaling data, suggests that the microtubule cytoskeleton may facilitate IRS-2 access to downstream effectors such as AKT.

Nonetheless, the data reveal that IRS-2 expression sensitizes breast carcinoma cells to apoptosis in response to treatment with microtubule-disrupting drugs, identifying IRS-2 as a possible biomarker for the response of the breast cancer to patients undergoing drug treatment ‘Vinca alkaloid’.

Mercado Matos stimulated with IGF-1 following short-term treatment (30 min to 1 h) with paclitaxel (Taxol) or nocodazole and measured the phosphorylation status of AKT, a downstream signaling effector of PI3K because IRS proteins are necessary for the recruitment and activation of PI3K by IGF-1R (4, 5, 26) that under Taxol treatment there was no alteration, while the interruption of the microtubule cytoskeleton in response to treatment with nocodazole significantly reduced the phosphorylation of AKT at both backbone 308 and serine 473.

“We demonstrated a differential involvement of the microtubule cytoskeleton in IRS-dependent activation of AKT. Activation of AKT in response to IGF-1 stimulation is maintained when the microtubule cytoskeleton is disrupted in cells signaling only through the IRS-1”, says the doctor.

Beginnings and interests in medicine

“My interest in cancer began when I was 17 years old, my brother -Raúl Mercado Matos- was diagnosed with cancer -synovial sarcoma- when he was 21 years old, and it made me curious to know more, especially in the area of ​​metastasis. I started my bachelor’s degree in biology at the University of Puerto Rico and I started doing research,” said the doctor, a Puerto Rican who recently obtained his doctorate from the physician-scientist program at the University of Massachusetts Medical School.

By way of background, Mercado Matos finished high school and later moved to Maryland where the National Institutes of Health (NIH) is located and had the opportunity to work with prominent researchers such as Dr. Phillip A. Dennis of the National Cancer Institute in lung with which he collaborated in the development of new treatments for this disease.

After two years, he applied to join the medical science program and moved to the city of Worcester where he began his career in medicine, combined with a doctoral degree in cancer biology.

“I started in 2010 and I graduated now in 2019. I am starting a residency in general surgery and in the future I would like to specialize in oncological surgery,” he explained in a conversation with the Journal of Medicine and Public Health.

Although his brother died at the age of 25, this doctor continued to be motivated by knowing in detail the behavior of the terrible disease when it metastasizes. However, although synovial sarcoma is a low-incidence cancer, he tried to get to know it in depth. However, research opportunities were few.

Due to this, he decided to contribute to medicine in research on breast cancer and others that, perhaps in the future “with my knowledge and experiences I can contribute to this type of cancer,” he said.

future studies

During the conversation with this medium, he did not rule out the possibility of returning to his hometown of Aibonito and finding out “what are the environmental factors that contribute to the high incidence of cancer” there, assured the 32-year-old scientist.

For now, he will remain focused on his general surgery residency that will take five years to prepare, but he was emphatic that he misses the culture and his family on the island.