TFF3 expression

Inhibition of TFF3 by a small molecule inhibitor not only enhanced EGFR-TKI sensitivity in LUAD cells but also restored the sensitivity of acquired EGFR-TKI resistant LUAD cells to EGFR-TKIs in vitro and in vivo. These findings demonstrate a pivotal function of TFF3 in mediating both intrinsic and acquired EGFR-TKI resistance in LUAD and may offer a potential therapeutic mechanism for delaying or overcoming resistance to EGFR-TKIs.

At a cut-off value of 5.9 ng/ml, serum TFF3 had a diagnostic sensitivity and specificity for CRC of 82% and 90%, respectively. In conclusion, serum TFF3 may be used as a non-invasive biomarker to predict disease activity in UC both alone and in combination with CRP and FC and it could have a potential role in diagnosis of CRC.

Of these, LGR5, which is particularly associated with lack of goblet cell features, may function in the control of differentiation rather than direct control of cell growth, as has so far mostly been assumed. These results emphasize the importance of methylation changes in driving cancer progression.

SPINK1 expression was predominantly observed in a subgroup of cancers that expressed TFF3. Our results call for screening these biomarkers for grading and molecular subtyping of the disease.

Hence, AMPC restored the sensitivity of tamoxifen and enhanced the efficacy of Taxanes in tamoxifen-resistant ER + MC. In conclusion, pharmacological inhibition of TFF3 may serve as an effective combinatorial therapeutic strategy for the treatment of tamoxifen-resistant ER + MC.

Activated STAT3 bound to PTGER4 promoter, the gene encoding for EP4, and facilitated PTGER4 transcription. TFF3 promotes clonogenic survival of CRC cells via upregulating EP4 expression.

Correlation analysis showed a strong negative correlation between TFF1 and TFF3 levels to IC50 values of palbociclib and abemaciclib. Our results identified and validated the common biomarkers, TFF1 and TFF3, as predictors of CDK4/6i response efficacy in ER-positive, HER2-negative BC patients. These findings provide a predictive tool capable of selecting de novo metastatic BC patients who will have the greatest benefit from the combination of CDK4/6i with endocrine treatment. Furthermore, our discovery of biomarkers in early versus late progression on CDK4/6i therapy will enable new therapeutic avenues and provide the rationale for future large-scale clinical trials.

In conclusion, serum and urinary TFF levels are promising predictive biomarkers, and their measurements provide a useful in vivo and non-invasive diagnostic screening tool. In particular, TFF1 and TFF3 could be surrogate markers of clinicopathological profiles of human lung cancer.

Leptin-induced TFF3 induction was markedly suppressed by inhibitors of PI3K (LY294002) and EGFR (Erlotinib). Together, these results suggest a novel role of LepR-mediated signaling in transactivating EGFR that leads to TFF3 expression via the PI3K-Akt pathway. Therefore, this study sheds light on the identification of potentially new therapeutic targets for the treatment of pre-cancerous symptoms in stomach and colorectum.

Furthermore, in mice bearing ER+ MC cell-generated xenografts, AMPC treatment significantly impeded xenograft growth. Hence, AMPC exemplifies a novel mechanism by which small molecule drugs may inhibit a dimeric oncogenic protein and provides a strategy to impede TFF3-dependent cancer progression.

These results also disclosed a novel relationship between TFF3 expression and the activation of the HIF‑1α/VEGFA signaling pathway. In summary, this study uncovered new insight into the mechanisms of TFF3's anti‑tumor activities in pituitary adenoma cells by investigating its effects on HIF‑1α/VEGFA signaling pathway regulation.

Combined pharmacological inhibition of TFF3 and WNT signaling significantly attenuated PDAC xenograft growth and potentiated the therapeutic efficacy of gemcitabine in both ex vivo and in vivo models. Hence, a mechanistic basis for combined inhibition of pathways enhancing PDAC progression is provided and suggests that inhibition of TFF3 may assist to ameliorate outcomes in PDAC.

In addition, we found that DEHP inhibited paclitaxel and doxorubicin effects in breast cancer cell lines MCF-7 and MDA-MB-231 and in zebrafish and mouse tumor initiation models. DEHP mediated AhR-related alterations in estrogen receptor expression through the ubiquitination system, which decreased tamoxifen effects in AhR knockout mice. These findings suggest a novel therapeutic avenue by targeting AhR in drug-resistant and recurrent breast cancer.

Our results show that the expression of TFF3 in lung cancer was obviously increased. Silencing TFF3 in SPC-A1 cells can inhibit the cell proliferation and promote cell apoptosis. At the same time, we confirmed that silencing TFF3 gene can inhibit the abnormal activation of Wnt/β-catenin signaling pathway in SPC-A1 cells.

TFF3 and FCGBP are coexpressed in PTC, and patients with lower gene expression had worse disease-free survival but higher immune cell infiltration. TFF3 was significantly underexpressed and may function with FCGBP synergistically in PTC.

We found that the levels of IL-6, p-JAK2/JAK2, and pSTAT3/STAT3 were inhibited in the pcDNA-TFF3 group compared to the pcDNA-NC group and these factors were upregulated in the si-TFF3 group compared to the si-NC group in BCPAP and TPC-1 cells. TFF3 inhibits thyroid cancer cell progression related to IL-6/JAK/STAT3 signaling pathway.

ConclusionTFF3 may be a promising biomarker for GC, and the TFF3 expression is likely to be involved in the invasion, metastasis, and differentiation of GC, which has a potential function to access the clinicopathological significance of GC in clinical practices.

In vitro and immunohistochemical assays using clinical samples demonstrated that TFF3 expression was associated with lung adenocarcinoma invasiveness. To the best of our knowledge, the current study is the first to report that TFF3 expression was associated with the histologic subtypes of lung adenocarcinoma.

Our findings demonstrate low expression of TFF3 in CRCs. Association between low TFF3 and histopathological features suggests involvement of this molecule in progression of CRC.

LINC00160-depleted MCF-7/Tax and BT474/Dox cells showed decreased tumour growth rates in nude mice. Overall, we identified a novel mechanism of LINC00160-mediated chemoresistance via the C/EBPβ/TFF3 axis, highlighting the potential of LINC00160 for treating BC with chemoresistance.

Finally, TFF3 was shown to regulate ATG12 in human colon adenocarcinoma cells in vitro. Thus, the data presented here suggest that both TFF3 and ATG12 may be promising potential therapeutic targets to develop novel treatment strategies for patients with colon adenocarcinoma.