Discovery of Cancer Protein Uncovers New Treatment Target

Researchers have identified how a specific protein, DUSP6, influences the growth and spread of colon cancer, offering new insights into why this type of cancer can be aggressive in certain patients. This discovery not only advances our understanding of colorectal cancer (CRC) but also reveals a promising treatment target.

Cancer cells rely on various molecules that regulate their growth and spread. Understanding these molecules, the pathways that control them, and how they become dysfunctional in cancer is crucial for both advancing knowledge and developing effective therapies.

Now, a team from the Yong Loo Lin School of Medicine at the National University of Singapore (NUS) has uncovered a significant role for the protein molecule DUSP6 in promoting CRC, the third most common cancer worldwide.

“In CRC, tumors contain higher levels of DUSP6, which accelerates cancer cell growth, enhances their ability to spread, and worsens patient outcomes,” explained Associate Professor Zhang Yongliang, from NUS Medicine’s Department of Microbiology and Immunology and the study’s lead author.

“This unexpected finding positions DUSP6 as a potential target for new treatments.”

DUSP6’s Complex Role in Cancer and Regulation of the MAPK Pathway

Although the relationship between DUSP6 and cancer has been studied before, its role varies by cancer type. DUSP6 regulates the mitogen-activated protein kinase (MAPK) pathway, which integrates external signals to control cell behaviors such as growth, proliferation, and survival. Specifically, DUSP6 modulates the activity of extracellular signal-regulated kinases 1 and 2 (ERK1/2) within the MAPK pathway.

Under normal conditions, ERK1/2 is activated by phosphorylation in response to MAPK pathway signals. As a phosphatase, DUSP6 deactivates ERK1/2 by removing phosphate groups, serving as a negative feedback mechanism to prevent overstimulation of the pathway. This balance ensures controlled cell growth and prevents harmful cellular behaviors.

However, DUSP6’s function in cancer varies depending on the type. For instance, in lung and nasopharyngeal cancers, as well as melanoma, DUSP6 suppresses tumor growth by inhibiting ERK1/2 activation. Conversely, in cancers such as gastric, cervical, ovarian, and glioblastomas, DUSP6 expression is associated with tumor growth. Its role in CRC, however, remained unclear until this study.

DUSP6’s Role in Cancer Growth and Metastasis Revealed Through Cell Engineering

Researchers engineered colon cancer cells to either overexpress or lack DUSP6. Cells with higher DUSP6 levels showed increased growth and migrated 60% faster, while cells without DUSP6 exhibited reduced growth and migration—key factors in cancer invasion. ERK1/2 activation decreased in DUSP6-overexpressing cells but increased in knockout cells.

Analysis of tumor samples from 81 CRC patients revealed higher DUSP6 levels in tumors compared to adjacent healthy tissues. Patients with elevated DUSP6 had worse survival rates, with a 20% lower survival rate at 60 months post-diagnosis.

“Our findings explain why some colon cancers are so aggressive and highlight DUSP6 as a promising target for new treatments,” Zhang stated, emphasizing the potential for therapies aimed at inhibiting DUSP6. This research advances understanding of CRC and offers a pathway for novel treatments.

Read Original Article: New Atlas

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