GATA6 in Pancreatic Cancer Initiation and Progression

Overview

Journal Genes Dis

Date 2024 Dec 24

PMID 39717718

Authors

Muyuan Ma

Jianhong An

Tingting Jiang

Keping Xie

Affiliations

Soon will be listed here.

Abstract

Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy characterized by insidious onset and lack of effective therapy. The molecular pathogenesis of PDA remains to be understood fully. Transcriptional factor GATA6 is an important transcriptional regulator in normal pancreas development, particularly in the initial specification and differentiation of the pancreas. Recent studies have linked pancreatic malignancy closely to GATA6. Increased levels of GATA6 expression enhance pancreatic cancer cell growth. GATA6 emerges as a lineage-specific oncogenic factor in PDA, augmenting the oncogenic phenotypes of PDA cells upon its overexpression. However, elevated GATA6 levels are correlated with well-differentiated tumors and a more favorable patient prognosis. Experimental evidence in genetic mouse models has revealed a tumor-suppressive role for GATA6. The circumstantial roles of GATA6 in pancreatic tumorigenesis remain to be defined. This review aims to elucidate recent advances in comprehending GATA6, emphasizing its crucial roles in both pancreas physiology and pathology. Special attention will be given to its involvement in PDA pathogenesis, exploring its potential as a novel biomarker and a promising therapeutic target for PDA.

References

Dijk F, Veenstra V, Soer E, Dings M, Zhao L, Halfwerk J . Unsupervised class discovery in pancreatic ductal adenocarcinoma reveals cell-intrinsic mesenchymal features and high concordance between existing classification systems. Sci Rep. 2020; 10(1):337. PMC: 6962149. DOI: 10.1038/s41598-019-56826-9. View

Fegert P, Blin N, Gott P . Transcription factor GATA-6 activates expression of gastroprotective trefoil genes TFF1 and TFF2. Biochim Biophys Acta. 2000; 1490(3):324-32. DOI: 10.1016/s0167-4781(00)00013-0. View

Nicolle R, Blum Y, Marisa L, Loncle C, Gayet O, Moutardier V . Pancreatic Adenocarcinoma Therapeutic Targets Revealed by Tumor-Stroma Cross-Talk Analyses in Patient-Derived Xenografts. Cell Rep. 2017; 21(9):2458-2470. PMC: 6082139. DOI: 10.1016/j.celrep.2017.11.003. View

Carrasco M, Delgado I, Soria B, Martin F, Rojas A . GATA4 and GATA6 control mouse pancreas organogenesis. J Clin Invest. 2012; 122(10):3504-15. PMC: 3461915. DOI: 10.1172/JCI63240. View

Rahib L, Smith B, Aizenberg R, Rosenzweig A, Fleshman J, Matrisian L . Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014; 74(11):2913-21. DOI: 10.1158/0008-5472.CAN-14-0155. View

Decker K, Goldman D, Grasch C, Sussel L . Gata6 is an important regulator of mouse pancreas development. Dev Biol. 2006; 298(2):415-29. PMC: 2824170. DOI: 10.1016/j.ydbio.2006.06.046. View

Martinelli P, Pau E, Cox T, Sainz Jr B, Dusetti N, Greenhalf W . GATA6 regulates EMT and tumour dissemination, and is a marker of response to adjuvant chemotherapy in pancreatic cancer. Gut. 2016; 66(9):1665-1676. PMC: 5070637. DOI: 10.1136/gutjnl-2015-311256. View

Bresnick E, Lee H, Fujiwara T, Johnson K, Keles S . GATA switches as developmental drivers. J Biol Chem. 2010; 285(41):31087-93. PMC: 2951181. DOI: 10.1074/jbc.R110.159079. View

Sakai Y, Nakagawa R, Sato R, Maeda M . Selection of DNA binding sites for human transcriptional regulator GATA-6. Biochem Biophys Res Commun. 1998; 250(3):682-8. DOI: 10.1006/bbrc.1998.9374. View

10.

Maeda M, Ohashi K, Ohashi-Kobayashi A . Further extension of mammalian GATA-6. Dev Growth Differ. 2005; 47(9):591-600. DOI: 10.1111/j.1440-169X.2005.00837.x. View

11.

Ketola I, Otonkoski T, Pulkkinen M, Niemi H, Palgi J, Jacobsen C . Transcription factor GATA-6 is expressed in the endocrine and GATA-4 in the exocrine pancreas. Mol Cell Endocrinol. 2004; 226(1-2):51-7. DOI: 10.1016/j.mce.2004.06.007. View

12.

Fonseca A, Kirkwood K, Kim M, Maitra A, Koay E . Intraductal Papillary Mucinous Neoplasms of the Pancreas: Current Understanding and Future Directions for Stratification of Malignancy Risk. Pancreas. 2018; 47(3):272-279. PMC: 5808987. DOI: 10.1097/MPA.0000000000000999. View

13.

Kardon D, Thompson L, Przygodzki R, Heffess C . Adenosquamous carcinoma of the pancreas: a clinicopathologic series of 25 cases. Mod Pathol. 2001; 14(5):443-51. DOI: 10.1038/modpathol.3880332. View

14.

Collisson E, Bailey P, Chang D, Biankin A . Molecular subtypes of pancreatic cancer. Nat Rev Gastroenterol Hepatol. 2019; 16(4):207-220. DOI: 10.1038/s41575-019-0109-y. View

15.

Martinelli P, Madriles F, Canamero M, Pau E, Del Pozo N, Guerra C . The acinar regulator Gata6 suppresses KrasG12V-driven pancreatic tumorigenesis in mice. Gut. 2015; 65(3):476-86. DOI: 10.1136/gutjnl-2014-308042. View

16.

Biankin A, Hudson T . Somatic variation and cancer: therapies lost in the mix. Hum Genet. 2011; 130(1):79-91. DOI: 10.1007/s00439-011-1010-0. View

17.

Tanaka H, Yanagisawa K, Shinjo K, Taguchi A, Maeno K, Tomida S . Lineage-specific dependency of lung adenocarcinomas on the lung development regulator TTF-1. Cancer Res. 2007; 67(13):6007-11. DOI: 10.1158/0008-5472.CAN-06-4774. View

18.

Alizadeh A, Eisen M, Davis R, Ma C, Lossos I, Rosenwald A . Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000; 403(6769):503-11. DOI: 10.1038/35000501. View

19.

Zhao J, Ohsumi T, Kung J, Ogawa Y, Grau D, Sarma K . Genome-wide identification of polycomb-associated RNAs by RIP-seq. Mol Cell. 2010; 40(6):939-53. PMC: 3021903. DOI: 10.1016/j.molcel.2010.12.011. View

20.

Hruban R, Takaori K, Klimstra D, Adsay N, Albores-Saavedra J, Biankin A . An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol. 2004; 28(8):977-87. DOI: 10.1097/01.pas.0000126675.59108.80. View