GATA6 Identified as a Key Factor in Pancreatic Cancer and a Potential Therapeutic Target
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GATA6 Identified as a Key Factor in Pancreatic Cancer and a Potential Therapeutic Target

23/02/2025 Compuscript Ltd
This new review article highlights the crucial role of GATA6, a transcription factor, in pancreatic ductal adenocarcinoma (PDA). The article explores GATA6’s dual role in cancer progression and its potential as a biomarker and treatment target.

Pancreatic cancer remains one of the deadliest malignancies, with a five-year survival rate of only 5%. This study finds that higher GATA6 expression correlates with better tumor differentiation and improved patient outcomes, while low GATA6 levels are linked to aggressive basal-like PDA, a chemotherapy-resistant subtype.

It is also revealed that GATA6 influences multiple cancer-related pathways—including Wnt, Notch, Hedgehog, TGF-β, and VEGFR—helping to regulate tumor development. While GATA6 overexpression can promote cancer growth, it also helps maintain epithelial differentiation, preventing tumor dedifferentiation and metastasis.

The authors suggest that GATA6 could serve as a biomarker for distinguishing PDA subtypes. Patients with low GATA6 expression are more likely to have treatment-resistant basal-like PDA, indicating a need for alternative therapies.

Notably, the findings suggest that GATA6-deficient tumors respond poorly to chemotherapy (such as FOLFIRINOX) but may benefit from targeted therapies involving the EGFR pathway. These insights could lead to more personalized treatment strategies, improving survival rates.

With pancreatic cancer accounting for 7% of all cancer-related deaths, this research advances the understanding of PDA progression and treatment response. The study underscores the need for further clinical trials to validate GATA6’s potential as a predictive biomarker and treatment target, paving the way for more effective precision medicine approaches.

Reference
Muyuan Ma, Jianhong An, Tingting Jiang, Keping Xie, GATA6 in pancreatic cancer initiation and progression, Genes & Diseases,
Volume 12, Issue 2, 2025, 101353.
DOI https://doi.org/10.1016/j.gendis.2024.101353
Journal Genes & Diseases

Genes & Diseases is a journal for molecular and translational medicine. The journal primarily focuses on publishing investigations on the molecular bases and experimental therapeutics of human diseases. Publication formats include full length research article, review article, short communication, correspondence, perspectives, commentary, views on news, and research watch.

Funding Information:
Guangzhou Ruiqian Biotech Company (No. 20230330)
National Natural Science Foundation of China (No. 82072632)
Guangzhou Municipality Bureau of Science and Technology (China) (No. 202102010033)
Natural Science Foundation of Guangdong Province, China (No. 2022A1515012585)

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Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.
Scopus CiteScore: 7.3
Impact Factor: 6.9

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All issues and articles in press are available online in ScienceDirect (https://www.sciencedirect.com/journal/genes-and-diseases ).
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Print ISSN: 2352-4820
eISSN: 2352-3042
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Muyuan Ma, Jianhong An, Tingting Jiang, Keping Xie, GATA6 in pancreatic cancer initiation and progression, Genes & Diseases,Volume 12, Issue 2, 2025, 101353.
https://doi.org/10.1016/j.gendis.2024.101353
Fichiers joints
  • Image Caption: Major signaling pathways associated with GATA6 and pancreas. Wnt antagonist dickkopf1 (DKK1) is a target gene of GATA6, and GATA6 can promote the development and carcinogenesis of the pancreas by activating the Wnt pathway via repressing of DKK1. GATA6 can also regulate the pancreatic endoderm specification through hedgehog signaling by inhibiting sonic hedgehog (Shh), in company with GATA4. GATA6 is the downstream target of the transforming growth factor-β (TGF-β) pathway, and the expression changes of GATA6 can affect the differentiation of pancreatic cells and the self-renewal of pancreas progenitor. In addition, GATA6 can affect the maintenance of intestinal epithelial and goblet cell differentiation by regulating Notch signaling. GATA6 regulates the lymphatic dissemination of bladder cancer through vascular endothelial growth factor receptor (VEGFR) signaling, which may also be associated with the initiation and progression of pancreatic cancer.Image credit: The authorsImage link: https://ars.els-cdn.com/content/image/1-s2.0-S2352304224001508-gr2_lrg.jpg License type: CC BY-NC-ND
  • Image Caption: The GATA proteins with different Zinc finger domains, and the sequence comparison of GATA6 from different species. The full length of GATA1, 2, 3, 4, 5, and 6 contains the two Zinc finger domains (N-ZF and C-ZF). The sequences of GATA6 protein from human, mouse and rat are aligned together. The Zinc finger region is boxed and the N-finger and C-finger are underlined. N-ZF, N-Zinc finger domain; C-ZF, C- Zinc finger domain; H, human; M, mouse; R, rat.Image credit: The authorsImage link: https://ars.els-cdn.com/content/image/1-s2.0-S2352304224001508-gr1_lrg.jpg License type: CC BY-NC-ND
23/02/2025 Compuscript Ltd
Regions: Europe, Ireland, Asia, China
Keywords: Health, Medical

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