GATA6 expression

HOTAIR activated RELA to upregulate miR-181a during hypoxia. Exosomal miR-181a promotes tumor angiogenesis by downregulating GATA6.

However, GATA6's prognostic significance is numerically lower after gemcitabine-based neoadjuvant chemoradiotherapy compared to its significance in patients treated with upfront surgery...Tumors highly expressing GATA6 show reduced infiltration of immunosuppressive regulatory T cells and M2 macrophages but increased infiltration of immune-stimulating, antigen-presenting, and activated T cells. Our findings caution against solely relying on GATA6 for molecular subtyping in clinical trials and open avenues for exploring immune-based combination therapies.

In this work, it was revealed that PLAU is a novel oncogene for LUSC and a new molecular regulatory mechanism of GATA6 in LUSC was unveiled. Targeting the GATA6/PLAU pathway might help in the development of novel therapeutic treatment strategies for LUSC.

During the occurrence and development of gastric cancer, the overexpression of FTO may inhibit the expression of GATA6-AS1, thus promoting the proliferation and metastasis of gastric cancer.

Our study provides crucial insights into the metabolic regulation of GATA6 in lung cancer cells. These findings have the potential to offer a solid theoretical foundation for the development of novel clinical treatments for lung cancer.

The activation of CFTR by GATA6 hampered LUAD progression by modulating the AA metabolism pathway, suggesting that GATA6/CFTR axis might be a therapeutic target for LUAD patients.

GATA6-AS1 inhibited the expression of fat mass and obesity-associated protein (FTO), an N6-methyladenosine (m6A) eraser, and repressed SNAI1 mRNA stability in an m6A-dependent manner. Our data suggested that GATA6-AS1 can inhibit PDAC cell proliferation, invasion, migration, EMT process and metastasis under hypoxia, and disrupting the GATA6-AS1/FTO/SNAI1 axis might be a viable therapeutic approach for refractory hypoxic pancreatic cancers.

Besides, MEG3 silencing could abrogate niraparib-mediated tumor growth inhibition in mice. Niraparib restrains prostate cancer cell proliferation and metastasis and tumor growth in mice by regulating the lncRNA MEG3/miR-181-5p/GATA6 pathway.

© 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

P=N/A, N=84, Active, not recruiting, University Health Network, Toronto | Recruiting --> Active, not recruiting | Phase classification: P2 --> PN/A

SMAD4 alterations were not associated with poor clinico-pathological features such as poor tumor grade, advanced tumor stage, positive lymphovascular invasion (LVI), or positive perineural invasion (PNI), compared with SMAD4-wildtype. Given that SMAD4 mutations were not associated with GATA6 expression or Moffitt subtype in two independent molecularly characterized PDAC cohorts, distinct biomarker-defined clinical trials are necessary.

The LC score is an accurate and non-invasive option for early LC diagnosis and a valuable complement to LC screening procedures based on computed tomography.

In vitro and in vivo experiments confirmed that miR-10a-5p-mediated downregulation of GATA6 suppressed Akt pathway activation. Overall, our findings suggest that miR-10a-5p could be a novel therapeutic target for ovarian cancer, and targeting the miR-10a-5p/GATA6/Akt axis could improve outcomes in this patient population.

Specifically speaking, GATA6-AS1 acts as a competing endogenous RNA (ceRNA) of miR-543 to upregulate the expression of PTEN, thus inactivating AKT signaling pathway to inhibit GC progression. In conclusion, this study has manifested that GATA6-AS1 inhibits GC cell proliferation and migration as a sponge of miR-543 by regulating PTEN/AKT signaling axis, offering new perspective into developing novel GC therapies.

Our results indicated that overexpression of BCL11B amplifies GATA6 expression in hepatocellular carcinoma in vitro and in vivo that leads to anti-apoptotic signal activation, and induces resistance to chemotherapy, which influenced the postoperative prognosis.

Initial data suggests worse outcomes to FOLFIRINOX (FFX) compared with gemcitabine nab-Paclitaxel (GnP) in basal tumors... Our work represents the largest known real world molecular comparison of transcriptional subtypes of PC. Differential outcomes for patients with basal tumors treated with FFX versus GnP warrants further investigation in prospective studies.

Finally, we found GATA6 expression in skin metastases of gastrointestinal origin, whereas GATA6 was absent in metastases originating from breast or lung cancers. Overall, our work identified GATA6 immunostaining as a new diagnostic tool for sebaceous tumors.

Hyperglycemia induce metabolic reprogramming into a glycolytic phenotype and promote EMT via the YAP/TAZ-Hedgehog signaling axis in PDAC. Hyperglycemia as an initial symptom may be the cause of highly invasive and metastatic potential by inducing YAP/TAZ overexpression, while YAP/TAZ could be a novel therapeutic target in PDAC patients.

Hyperglycaemia induces metabolic reprogramming into glycolytic phenotype and promotes EMT via YAP/TAZ-Hedgehog signalling axis, and YAP/TAZ could be a novel therapeutic target in PDAC.

The expression of GATA4 and GATA6 was related to DFS, being more favorable in the GATA4+/GATA6+ group. The determination of the expression of GATA4 and GATA6 by IHC is feasible and provides complementary clinical and prognostic information that can help improve the stratification of patients with PDAC.

In conclusion, GATA6 and CK5 immunohistochemical expression phenotypes may stratify the survival of patients with NAC-PCs and reflect post-NAC phenotypic transitions associated with poor prognosis. Prompt evaluation of immunohistochemical phenotypes may contribute to designing a precision therapeutic strategy for patients with PCs.

Mechanistic studies showed that SNHG7 acted as a competitive endogenous RNA to sponge miR-181a-5p to regulate the expression of GATA6, thereby promoting ATB resistance in ATB-resistant cell lines. In conclusion, SNHG7 plays an important role in ATB resistance, and it may be used to monitor ATB resistance in CRC.

In addition, annexin A10 (ANXA10) which is the largest type of Ca-regulated phospholipid-binding protein in eukaryotic cells was detected as a target gene for GATA6 and ANXA10 suppressed Vimentin expression in EMT in OSCC. Therefore, the GATA6/ANXA10 cascade may be a potential therapeutic approach for the treatment of lymph node metastases in OSCC patients.

Classical genomic profiling destroys tissue architecture hampering the ability to study mutant KRAS expression at single cell level. We report the feasibility of successfully staining KRASG12D by BaseScope technology on clinical samples and relate it to molecular subtype and functional markers, providing novel insights into tumor heterogeneity and plasticity

GATA4 and GATA6 cooperate to maintain the classical phenotype. Our findings provide compelling rationale to assess their expression as biomarkers of poor prognosis and therapeutic response.

In addition, we also observed that circ_0008717 could regulate GATA6 expression by sponging miR-326. Circ_0008717 promoted breast cancer growth and metastasis through miR-326/GATA6 axis, revealing a potential therapeutic target for breast cancer treatment.

These results demonstrate that there is an inversely correlated relationship between endometrial GATA2 and GATA6 levels with adenomyosis patients having diminished GATA2 and concurrent elevated GATA6 levels. In vitro results showing lower GATA2 and higher GATA6 levels, together with decreased PGR and PRL mRNA levels in HESCs from adenomyosis patients, supports impaired decidualization. IMPACT STATEMENT: Dysregulated expression of the inversely related GATA2 and GATA6 transcription factors contribute to adenomyosis associated implantation failure leading to infertility.

Further evaluation confirmed that LMP2A induces ETV5 transcription, but repress GATA6 and NOTCH3 expression. ETV5, GATA6 and NOTCH3 are the candidate targets of LMP2A in gastric cancer.

Mechanistically, loss of EP300 directly down-regulated GATA6 expression, thereby silencing the GATA6-regulated differentiation program and leading to a phenotypic transition from the classical subtype to the dedifferentiated basal-like/squamous subtype of pancreatic cancer. EP300 mutation and loss of GATA6 function bypassed the anti-differentiation activity of Wnt signaling, rendering these cancer cells resistant to Wnt inhibition. .

The genetic variation and interaction of the GATA family may be closely related to the pathogenesis and prognosis of OC, and the regulatory network composed of GATA family genes and their neighboring genes are mainly involved in Notch signaling pathway, Th1 and Th2 cell differentiation and Hippo signaling pathway. Transcriptional GATA1/2/3/4/6 could be prognostic markers and potential therapeutic target for OC patients.

In conclusion, the findings of the present study demonstrated that GATA6 promoted the malignant development of OSCC cells by binding to the FN1 promotor. These results may contribute to further understanding the pathogenesis of OSCC and provide potential therapeutic targets for the clinical treatment of OSCC.

Furthermore, global knockout of TLR9 or specific knockout of TLR9 in FRC diminished the beneficial effect of ODN1585 and anti-PD-1 combined treatment on tumor burden and survival. These data demonstrate the potential utility of the FRC-TLR9 signaling in modulating PRM retention to improve the therapeutic efficacy of ICB in peritoneal tumors.

Serum levels of miR-200a-3p >1.475 and GATA6 <1.195 may assist the early diagnosis of NSCLC. GATA6 may function in NSCLC as a miR-200a-3p target, which may provide a future reference for NSCLC early diagnosis and treatment.

This hypothesis is further being explored in resectable PDAC in the NeoPancONE trial (NCT04472910). The COMPASS dataset is rich for discovery leading to 26 abstracts and 12 manuscripts to date, 3 ongoing new trials and over 80 international collaborative agreements.

Here again, when treating established tumors, the combination of cisplatin with the HSP90 inhibitor onalespib was highly effective and almost completely prevented further tumor growth. We propose that the combination of platinum drugs and HSP90 inhibitors might be worth testing in the clinics for the treatment of cisplatin-resistant PDACs.

Adjuvant FOLFIRINOX (mFFX) in resected PDAC has been proven to improve overall survival (OS) relative to adjuvant gemcitabine...To date, 23 pts have been recruited. The study duration will be five years.