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.