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Pancreatic cancer hijacks a brain-building protein

Date:
February 14, 2024
Source:
Cold Spring Harbor Laboratory
Summary:
Scientists have discovered that pancreatic ductal adenocarcinoma (PDAC) hijacks a protein called EN-1 to evade cancer-fighting genes during metastasis. Future drugs targeting EN-1 or related proteins in cancer cells could lead to better, more personalized treatments.
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Scientists at Cold Spring Harbor Laboratory (CSHL) and the University of California, Davis have reached a new breakthrough in pancreatic cancer research -- eight years in the making. It could help slow the disease's deadly spread.

In 2017, as a postdoc in CSHL's Tuveson lab, Chang-il Hwang and collaborators from the Vakoc lab uncovered a protein essential for jumpstarting metastasis in pancreatic ductal adenocarcinoma (PDAC). Now an assistant professor at UC Davis, Hwang recently reunited with CSHL Professors David Tuveson and Christopher Vakoc. The trio once again set their sights on PDAC. The disease is known for its aggressiveness. It often spreads to other organs like wildfire, wreaking havoc in its path.

"Metastatic spread is one of the reasons pancreatic cancer is such a deadly disease," Vakoc says. "Our study led by Dr. Hwang has opened the door to new insights we might one day use to combat aggressive PDAC."

The team found that late-stage PDAC hijacks a protein called Engrailed-1 (EN-1) to evade the body's natural cancer defenses. EN-1 is a type of protein known as a transcription factor. These proteins control the timing and duration of gene expression. This particular transcription factor is required to form major areas of the brain.

"EN-1 is known to play a role in neurodevelopment," Hwang explains. "In the pancreas, it's not normally expressed. But in the later stages of pancreatic cancer, it gets overly expressed and makes the cancer more metastatic." That means a faster, deadlier spread. But what if EN-1 could be targeted in cancer? Hwang, Tuveson, and Vakoc sought to find out.

The team used organoids -- mini versions of tumors -- to identify the role of over-expressed EN-1 in PDAC. They found that higher levels of the aberrant protein blocked genes associated with natural cell death. When EN-1 expression was curtailed, the genes it targets were able to do their job, promoting healthy cell survival.

"Without EN-1, cancer progression slows," Hwang says. "At the moment, it's hard to target transcription factors with drugs. But in the future, it may be possible to disrupt the kind of interactions we see with mutated EN-1 in PDAC."

Pancreatic cancer remains the third-leading cause of cancer-related deaths in the U.S. Hwang plans to continue collaborating with CSHL in hopes that his team's work may lead to better treatments.

"We know certain types of PDAC are dependent on EN-1," Hwang says. "If we can develop a way to test for it, we can create more personalized therapeutics and treatment strategies for patients. We're looking forward to heading in that direction."


Story Source:

Materials provided by Cold Spring Harbor Laboratory. Original written by Nick Wurm. Note: Content may be edited for style and length.


Journal Reference:

  1. Jihao Xu, Jae‐Seok Roe, EunJung Lee, Claudia Tonelli, Keely Y. Ji, Omar W. Younis, Tim D.D. Somervile, Melissa Yao, Joseph P. Milazzo, Herve Tiriac, Anna M. Kolarzyk, Esak Lee, Jean L. Grem, Audrey J. Lazenby, James A. Grunkemeyer, Michael A. Hollingsworth, Paul M. Grandgenett, Alexander D. Borowsky, Youngkyu Park, Christopher R. Vakoc, David A. Tuveson, Chang‐Il Hwang. Engrailed‐1 Promotes Pancreatic Cancer Metastasis. Advanced Science, 2023; 11 (6) DOI: 10.1002/advs.202308537

Cite This Page:

Cold Spring Harbor Laboratory. "Pancreatic cancer hijacks a brain-building protein." ScienceDaily. ScienceDaily, 14 February 2024. <www.sciencedaily.com/releases/2024/02/240214122623.htm>.
Cold Spring Harbor Laboratory. (2024, February 14). Pancreatic cancer hijacks a brain-building protein. ScienceDaily. Retrieved April 13, 2024 from www.sciencedaily.com/releases/2024/02/240214122623.htm
Cold Spring Harbor Laboratory. "Pancreatic cancer hijacks a brain-building protein." ScienceDaily. www.sciencedaily.com/releases/2024/02/240214122623.htm (accessed April 13, 2024).

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