Trefoil factor 3 contributes to the malignancy of glioma via regulating HIF-1α

Diao, Shuo; Zheng, Qianqian; Gao, Jian; Yao, Yu; Ren, Siyang; Liu, Yongjian; Xu, Yunhua

doi:10.18632/oncotarget.20010

Cited by 8 publications

(5 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, TFF3 has been implicated in reduced sensitivity and acquired resistance to chemo-, hormonal, and targeted therapies in different cancers; and in particular, mammary carcinoma with acquired trastuzumab resistance exhibited a shift in oncogene addiction from HER2 to TFF3 8,10,21 . As TFF3 exhibits increased expression in various cancers to promote cancer progression, therapeutic resistance, and relapse, and is associated with poor patient survival, it is a potential actionable target in cancer 9,11–13,33,34 . Hence, we have designed a novel small-molecule inhibitor of TFF3, AMPC (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%

A novel small-molecule inhibitor of trefoil factor 3 (TFF3) potentiates MEK1/2 inhibition in lung adenocarcinoma

et al. 2019

View full text Add to dashboard Cite

TFF3 has been identified as a novel biomarker to distinguish between lung adenocarcinoma (ADC) and lung squamous-cell carcinoma (SCC). Herein, we determined the oncogenic functions of TFF3 and demonstrated the potential of pharmacological inhibition of TFF3 in lung ADC using a novel small-molecule inhibitor of TFF3 dimerization (AMPC). Forced expression of TFF3 in lung ADC cells enhanced cell proliferation and survival, increased anchorage-independent growth, cancer stem cell behavior, growth in 3D Matrigel, and cell migration and invasion. In contrast, depleted expression of TFF3 suppressed these cellular functions. Mechanistically, TFF3 exerted its oncogenic function through upregulation of ARAF and hence enhanced downstream activation of MEK1/2 and ERK1/2. Pharmacological inhibition of TFF3 by AMPC, resulted in markedly decreased cell survival, proliferation, 3D growth and foci formation, and impaired tumor growth in a xenograft mouse model. Moreover, the combination of various MEK1/2 inhibitors with AMPC exhibited synergistic inhibitory effects on lung ADC cell growth. In conclusion, this study provides the first evidence that TFF3 is a potent promoter of lung ADC progression. Targeting TFF3 with a novel small-molecule inhibitor alone or in combination with conventional MEK1/2 inhibitors are potential strategies to improve the outcome of lung ADC.

show abstract

Section: Discussionmentioning

confidence: 99%

A novel small-molecule inhibitor of trefoil factor 3 (TFF3) potentiates MEK1/2 inhibition in lung adenocarcinoma

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Hypoxia elicits nuclear accumulation of HIF‐1α, which binds to the consensus HRE sequence located within the TFF3 promoter 7 . Knockdown of TFF3 reduced the expression of HIF‐1α in a hypoxia‐independent manner 29 . Considering their tight relationship to both ER and HIF, we first noticed that there was a significant correlation between CA12 and TFF3.…”

Section: Discussionmentioning

confidence: 89%

“…Knockdown of TFF3 reduced the expression of HIF-1α in a hypoxiaindependent manner 29 . Considering their tight relationship to both ER and HIF, we first noticed that there was a significant correlation ESR1 on protein level.…”

Section: Discussionmentioning

confidence: 99%

Correlation between CA12 and TFF3 and their prediction value of neoadjuvant chemotherapy response in breast cancer

Shen

Yang

Lei

et al. 2022

Clinical Pharmacy Therapeu

View full text Add to dashboard Cite

What is known and Objective: Compared with other molecular subtypes, hormone receptor-positive breast cancer often shows worse neoadjuvant chemotherapy efficacy. This study aims to explore the relationship between the oestrogen receptor (ER)-related genes carbonic anhydrase 12 (CA12) and trefoil factor 3 (TFF3) and their predictive value of neoadjuvant chemotherapy for breast cancer. Methods:We investigated the relationships between CA12, TFF3 and ER status and their predictive value of anthracycline-taxane neoadjuvant chemotherapy in 115 female breast cancer patients via real-time polymerase chain reaction (RT-PCR) and 4 GEO datasets: GSE41998, GSE25065, GSE20194 and GSE20271. Then, the effects of CA12 and TFF3 on the chemotherapy drugs doxorubicin and docetaxel were verified in vitro in the breast cancer cell lines MCF-7 and BT474.

show abstract

“…However, VHL-defective ccRCC cell lines display unexpectedly variable sensitivity to HIF-2α-targeted therapies [ 11 ], which provide effective treatment for only a subset of patients [ 140 ]. Mechanistically, phosphorylation of HIF-1α has been demonstrated to enhance transactivation of target genes by either disrupting its interaction with VHL and thereby stabilizing HIF-1α, or by increasing the affinity of HIF-1α for transcriptional coactivators [ 141 ]. We showed that CK2 associates with and retains its catalytic activity towards HIF-2α, suggesting a functional link between them.…”

Section: Discussionmentioning

confidence: 99%

Cooperative Blockade of CK2 and ATM Kinases Drives Apoptosis in VHL-Deficient Renal Carcinoma Cells through ROS Overproduction

Giacosa

Pillet

Séraudie

et al. 2021

Cancers

View full text Add to dashboard Cite

Kinase-targeted agents demonstrate antitumor activity in advanced metastatic clear cell renal cell carcinoma (ccRCC), which remains largely incurable. Integration of genomic approaches through small-molecules and genetically based high-throughput screening holds the promise of improved discovery of candidate targets for cancer therapy. The 786-O cell line represents a model for most ccRCC that have a loss of functional pVHL (von Hippel-Lindau). A multiplexed assay was used to study the cellular fitness of a panel of engineered ccRCC isogenic 786-O VHL− cell lines in response to a collection of targeted cancer therapeutics including kinase inhibitors, allowing the interrogation of over 2880 drug–gene pairs. Among diverse patterns of drug sensitivities, investigation of the mechanistic effect of one selected drug combination on tumor spheroids and ex vivo renal tumor slice cultures showed that VHL-defective ccRCC cells were more vulnerable to the combined inhibition of the CK2 and ATM kinases than wild-type VHL cells. Importantly, we found that HIF-2α acts as a key mediator that potentiates the response to combined CK2/ATM inhibition by triggering ROS-dependent apoptosis. Importantly, our findings reveal a selective killing of VHL-deficient renal carcinoma cells and provide a rationale for a mechanism-based use of combined CK2/ATM inhibitors for improved patient care in metastatic VHL-ccRCC.

show abstract

Trefoil factor 3 contributes to the malignancy of glioma via regulating HIF-1α

Cited by 8 publications

References 42 publications

A novel small-molecule inhibitor of trefoil factor 3 (TFF3) potentiates MEK1/2 inhibition in lung adenocarcinoma

A novel small-molecule inhibitor of trefoil factor 3 (TFF3) potentiates MEK1/2 inhibition in lung adenocarcinoma

Correlation between CA12 and TFF3 and their prediction value of neoadjuvant chemotherapy response in breast cancer

Cooperative Blockade of CK2 and ATM Kinases Drives Apoptosis in VHL-Deficient Renal Carcinoma Cells through ROS Overproduction

Contact Info

Product

Resources

About