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JESSICA A. BURGOS BSN 3-B
 Two Proteins Work in Tandem to Build Lifelines to Cancer Cells, Study Finds
Emily Henderson, B. Sc. (September 20,2021)

In human cancer cell and mouse studies, researchers from Johns Hopkins
Medicine have found that a set of proteins work in tandem to build supply lines that
deliver oxygen and nutrients to tumors, enabling them to survive and grow. The protein
twosome, PADI4 and HIF-1, ramp up their activity under low-oxygen conditions that are
typically found in a fast-growing tumor, allowing it to build new blood vessels that feed
the cancer's growth.

The researchers say the discovery provides new avenues for developing anti-
cancer therapies that interfere with blood vessel development.

"The discovery gives us an opportunity to find combinations of existing or new

drugs that target these pathways to treat cancer and prevent drug resistance," says
Gregg Semenza, M.D., Ph.D., the C. Michael Armstrong Professor of Genetic Medicine,
Pediatrics, Oncology, Medicine, Radiation Oncology and Biological Chemistry at the
Johns Hopkins University School of Medicine. Semenza also serves as director of the
Vascular Program at the Johns Hopkins Institute for Cell Engineering.

Semenza shared the 2019 Nobel Prize in Physiology or Medicine for the
discovery of how HIF-1 controls the ability of cells to adapt to low oxygen levels. His lab
and others have found that HIF-1 (hypoxia-inducible factor 1) activates more than 5,000
genes under low-oxygen conditions. However, it was unclear precisely how HIF-1
turned on those genes to spur blood vessel growth.

Within the cell, DNA is negatively charged, which allows it to interact with
positively charged proteins called histones. The DNA is wound like a spool of thread
around the histones when it is not being used.

Specifically, Semenza says, PADI4 incites a reaction that causes the histones to
lose their positive charge, allowing the DNA to unwind.

To explore the partnership between HIF-1 and PADI4, the researchers studied
human breast and liver cancer cells grown in the laboratory. The researchers first
interfered with the cells' ability to produce PADI4, and then exposed the cells to low
oxygen conditions for 24 hours. By analyzing gene activity within these cells, the
researchers found that 87% of the 1,300 genes turned on by HIF-1 in response to
hypoxia were not turned on in cells lacking PADI4 protein.

The researchers then injected the cancer cells into the breast tissue of mice and
tracked tumor growth. Tumors without PADI4 were five times smaller and developed
five times fewer blood vessels compared with tumors formed from cells with normal
levels of PADI4. This showed that in a living organism, elimination of PADI4 impaired
the tumor's ability to grow.

The findings in mice, say the researchers, allow them to tie together studies from
human cancers where higher HIF-1 activity in patients' primary tumor biopsies
correlates with higher rates of mortality.

INSIGHTS

This article discusses the findings of a conducted study by researchers from

Johns Hopkins Medicine about the two proteins – PADI4 and HIF-1 - that work together
to build lifelines for cancer cells. These proteins can survive and even ramp up their
activities in low-oxygen conditions. The article also explains how these proteins
contribute to the fast-growing of a tumor. And stating that elimination of PADI4 impaired
the tumor’s ability to grow.

Upon reading the article, it made me appreciate the importance of research more.
Especially, cancer research. Cancer research can span from cancer prevention to
laboratory research that examines new or improved ways to detect cancer or
developing new drugs to fight cancer, from clinical trials to quality-of-life research for
survivors. In short, it is crucial to improve the prevention, detection, and treatment of
these cancers, and ensure that survivors live longer, better lives. This also identifies the
causes of cancer, like the mentioned research study above, and is pointing the way to
improved methods of diagnosis and treatment.

This kind of research will surely help us fight cancer considering that in our
country – Philippines, Cancer remains one of the leading causes of death among
Filipinos according to the Philippine Statistics Authority. Second leading cause of death
because a total of 62,289 Filipinos died of cancer in 2020. Most common cancers are
breast, lung, colorectal, liver, and prostate.

Discoveries from past research have led to a more effective treatments and
prevention strategies than before. But, doing further research, discovering more about
cancer will in turn save more lives from this disease.

Reference:

Henderson, E. (2021, September 20). Two Proteins Work in Tandem to Build Lifelines to Cancer Cells,
Study Finds. Retrieved from https://www.news-medical.net/news/20210920/Two-proteins-work-in-
tandem-to-build-lifelines-to-cancer-cells-study-finds.aspx