Exploring a protein’s role in lung cancer

M. Saeed Sheikh, MD, PhD (photo by Richard Whelsky)

M. Saeed Sheikh, MD, PhD (photo by Richard Whelsky)

This is one of a series of articles focusing on lung cancer.

BY AMBER SMITH

Work underway at Upstate is focused on a novel protein in lung cancer that could, potentially, help stimulate lung cancer cell death. It’s taking place in the lab of professor M. Saeed Sheikh, MD, PhD, thanks to a grant from the Michael E. Connolly Endowment for Lung Cancer Research, through the Upstate Foundation.

Mansi Babbar, PhD, completed her dissertation research in Sheikh’s lab,

characterizing a protein called Coiled-coil Helix Tumor and Metabolism-1, which is abbreviated to CHTM1. She earned her doctorate at Upstate and is now a postdoctoral fellow at the National Institutes of Health.

So, what’s important to know about CHTM1?

Some lung cancer cells are addicted to glutamine, the body’s most abundant amino acid. This is what a molecule of glutamine looks like.


Some lung cancer cells are addicted to glutamine, the body’s most abundant amino acid. This is what a molecule of glutamine looks like.

Sheikh’s team — which also included Ying Huang, MD, PhD, and Christopher Curtiss, MD— examined tissue samples from more than 230 patients with lung, breast or colon cancer and found elevated levels of this protein in the majority of samples.

In a series of additional experiments, they established a role for CHTM1 in cancer cell metabolism.

“It is known that certain cancer cells, including some lung cancer cells, are addicted to glucose and glutamine,” Sheikh says, describing glutamine as the body’s most abundant amino acid, needed for various building blocks, which cancer cells rely on as a nutrient for proliferation. “Deprivation of these nutrients leads to a type of stress known as metabolic stress.”

The researchers also discovered that a deficiency of CHTM1 makes lung cancer cells more sensitive to being killed by metabolic stress.

“Cancers are metabolically flexible,” Sheikh says, explaining that “in the absence of important nutrients, they appear to utilize markers to survive the metabolic stress induced by nutrient deprivation.

“We think CHTM1 is one such marker. It appears to help cancer cells grow during the early stages of development, when blood supply is not fully established and nutrients are scarce.”

Take away CHTM1, he says, “and we can increase lung cancer cell death during metabolic stress.”

A paper written by Babbar, Huang, Curtiss and Sheikh this year in the Journal of Experimental & Clinical Cancer Research describes their

approach and results for disabling this protein.

The Upstate team also notes that a deficiency of CHTM1 made lung cancer cells more sensitive to anticancer effects of metformin, a drug that helps people with diabetes control their blood sugar.

Researchers around the world became intrigued by metformin after doctors noticed that people who have taken the drug long term seem to have a lower incidence of cancer. Studies are underway to determine the cancer-fighting properties of metformin.

“There is a lot of enthusiasm about this drug,” Sheikh says.

He believes that with the CHTM1 protein disabled, metformin — or other, similar drugs — may prove to be more effective in fighting cancer.

Answers lead to new, intriguing questions

  • Higher levels of the protein CHTM1 are present in some lung cancers, as well as some breast cancers and colon cancers. Could this fact lead the way to the development of a biomarker, or biological indicator of disease?
  • Cancer cells become sensitized when levels of the protein CHTM1 are diminished. Would that help an anti-cancer drug become more effective?
  • The protein CHTM1 helps lung cancer cells grow during the early stages of development. Depriving fully developed lung cancer cells of certain nutrients creates metabolic stress, and they are more sensitive to death by metabolic stress when they lose CHTM1. If scientists induce metabolic stress and block CHTM1 at the same time, would that be a novel approach to kill lung cancer cells?

To donate to the Michael E. Connolly Endowment for Lung Cancer Research at Upstate, contact the Upstate Foundation at 315-464-4416.

Cancer Care magazine fall 2019 issue coverThis article appears in the fall 2019 issue of Cancer Care magazine.

 

 

 

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