Upregulation of Trefoil Factor 3 (TFF3) After Rectal Cancer Chemoradiotherapy Is an Adverse Prognostic Factor and a Potential Therapeutic Target

Casado, Enrique; Moreno, Víctor; Sánchez, José Javier; Pulgar, María Teresa Gómez del; Feliú, Jaime; Maurel, Joan; Castelo, Beatriz; Moreno-Rubio, Juan; López, R.; García‐Cabezas, Miguel Ángel; Burgos, Emilio; Castro, Javier de; Belda-Iniesta, Cristóbal; López-Gómez, Miriam; Gómez-Raposo, César; Zambrana, Francisco; Sereno, María; Fernández-Martos, Carlos; Vázquez, Pilar Díez; Lacal, Juan Carlos; González-Barón, Manuel; Cejas, Paloma

doi:10.1016/j.ijrobp.2012.01.083

Cited by 21 publications

(22 citation statements)

References 18 publications

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“…A large number of studies showed that the use of CRT, which is the combination of radiotherapy and chemotherapy is well described for cancer treatment [7,8]. Moreover, a large number of previous studies also revealed that some intrinsic genetic factors have significant influence on the prognosis of CRT [9,10]. In recent decades, an increasing number of studies indicating that CD133 expression may play an independent important role in tumor recurrence and the OS of cancer patients treated with CRT [9,11].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Prognostic value of CD133 expression in cancer patients treated with chemoradiotherapy: a meta-analysis

Zhai

et al. 2014

Tumor Biol.

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Many studies evaluated the correlations of CD133 expression with the clinical outcomes in patients treated with chemoradiotherapy (CRT) but yielded controversial results. This meta-analysis was performed to identify the impacts of CD133 expression on the prognosis of cancer patients treated with CRT. Electronic databases updated up to March 2014 were searched to find relevant studies. Relevant literatures without any language restrictions were searched via electronic databases as follows: Web of Science (1945 ~ 2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966 ~ 2013), EMBASE (1980 ~ 2013), CINAHL (1982 ~ 2013), and the Chinese Biomedical Database (CBM) (1982 ~ 2013). STATA software was used for the current meta-analysis. Hazard ratios (HR) and its corresponding 95% confidence interval (95% CI) were calculated. Six studies were identified with a total of 470 cancer patients treated with CRT. The meta-analysis results showed that CD133-positive patients had poorer overall survival (OS) than that of CD133-negative patients (HR = 2.13, 95% CI = 1.20 ~ 3.07, P < 0.001). Furthermore, CD133-positive patients displayed shorter disease-free survival (DFS) than that of CD133-negative patients (HR = 1.74, 95% CI = 0.08 ~ 3.40, P = 0.039). Ethnicity-stratified analysis indicated that CD133 expression positively correlated with shorter OS among the Japanese, Chinese, and Spanish populations (all P < 0.05). In conclusion, our findings suggest that CD133 expression may be positively correlated with poorer prognosis in cancer patients treated with CRT.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Prognostic value of CD133 expression in cancer patients treated with chemoradiotherapy: a meta-analysis

Zhai

et al. 2014

Tumor Biol.

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“…These genes encode for proteins secreted by goblet cells in the intestine, which play roles in innate intestinal immunity and response to injury (25–27). All have been linked to intestinal tumors in Apc Min/+ mice and human CRC (27–33). Tumor necrosis factor (ligand) superfamily, member 10 ( Tnfsf10 ) and Lipocalin 2 ( Lcn2 ) were overexpressed in intramucosal carcinoma relative to adenomas and are also linked to Apc Min/+ intestinal tumors and human CRC.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Tumor Growth Patterns in a Novel Murine Model of Colorectal Cancer

Olson

Hadac

Sievers

et al. 2014

Cancer Prevention Research

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Colorectal cancer (CRC) often arises from adenomatous colonic polyps. Polyps can grow and progress to cancer, but may also remain static in size, regress, or resolve. Predicting which progress and which remain benign is difficult. We developed a novel long-lived murine model of CRC with tumors that can be followed by colonoscopy. Our aim was to assess whether these tumors have similar growth patterns and histologic fates to human colorectal polyps to identify features to aid in risk-stratification of colonic tumors. Long-lived ApcMin/+ mice were treated with dextran sodium sulfate to promote colonic tumorigenesis. Tumor growth patterns were characterized by serial colonoscopy with biopsies obtained for immunohistochemistry and gene expression profiling. Tumors grew, remained static, regressed, or resolved over time with different relative frequencies. Newly developed tumors demonstrated higher rates of growth and resolution than more established tumors that tended to remain static in size. Colonic tumors were hyperplastic lesions (3%), adenomas (73%), intramucosal carcinomas (20%), or adenocarcinomas (3%). Interestingly, the level of β-catenin was higher in adenomas that became intratumoral carcinomas as compared to those that failed to progress. In addition, differentially expressed genes between adenomas and intramucosal carcinomas were identified. This novel murine model of intestinal tumorigenesis develops colonic tumors that can be monitored by serial colonoscopy, mirror growth patterns seen in human colorectal polyps, and progress to CRC. Further characterization of cellular and molecular features are needed to determine which features can be used to risk-stratify polyps for progression to CRC and potentially guide prevention strategies.

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“…As we know TFF3 is a soluble peptide containing trefoil domain and C-terminal dimerization domain which is not only a novel prognostic marker but also a therapeutic target in various cancers, such as mammary carcinoma, gastric cancer and prostate carcinoma [5–8]. Upregulation of TFF3 after rectal cancer chemo-radiotherapy is an adverse prognostic factor [9]. Furthermore, in prostate carcinoma cells, TFF3 reduces the sensitivity to ionizing-radiation [10].…”

Section: Introductionmentioning

confidence: 99%

“…TFF3 also may contribute to cancer metastasis with epithelial-to-mesenchymal transition (EMT) potentially through the regulation of genes such as androgen receptor (AR), FOXA1 and human epidermal growth factor receptor-type 2 (HER2) [12, 13]. Moreover, TFF3, a secreted protein, is a valuable predictive serum biomarker in patients with metastatic colorectal cancer [9]. In cancer cells, TFF3 promotes cell migration, invasion and metastasis by reducing cell–cell and cell–matrix interactions and enhancing cell scattering in bronchiole or other epithelia cells [14, 15].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of trefoil factor 3 (TFF3) contributes to the malignant progression in cervical cancer cells

Zhang

Chen

et al. 2017

Cancer Cell Int

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BackgroundThere remains a great need for effective therapies for cervical cancers, the majority of which are aggressive leaving patients with poor prognosis.Methods and resultsHere, we identify a novel candidate therapeutic target, trefoil factor 3 (TFF3) which overexpressed in cervical cancer cells and was associated with reduced postoperative survival. Functional studies demonstrated that TFF3 overexpression promoted the proliferation and invasion of cervical cancer cells, and inhibited the apoptosis by inducing the mRNA changes in SiHa and Hela cell lines. Conversely, TFF3 silencing disrupted the proliferation and invasion of cervical cancer cells, and induced the apoptosis via Click-iT EdU test, flow cytometry analysis and two-dimensional Matrigel Transwell analysis. Western blot analysis showed that overexpression of TFF3 repressed E-cadherin (CDH1) expression to promote the invasion of cervical cancer cells. Furthermore, down-regulated CDH1 via overexpression of TFF3 was significantly up-regulated by virtue of inhibitor of p-STAT3.ConclusionsThese results suggested that TFF3 stimulated the invasion of cervical cancer cells probably by activating the STAT3/CDH1 signaling pathway. Furthermore, overexpression of TFF3 decreased the sensitivity of cervical cancer cells to etoposide by increasing P-glycoprotein (P-gp) functional activity. Overall, our work provides a preclinical proof that TFF3 not only contributes to the malignant progression of cervical cancers and but also is a potential therapeutic target.Electronic supplementary materialThe online version of this article (doi:10.1186/s12935-016-0379-1) contains supplementary material, which is available to authorized users.

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Upregulation of Trefoil Factor 3 (TFF3) After Rectal Cancer Chemoradiotherapy Is an Adverse Prognostic Factor and a Potential Therapeutic Target

Cited by 21 publications

References 18 publications

RETRACTED ARTICLE: Prognostic value of CD133 expression in cancer patients treated with chemoradiotherapy: a meta-analysis

RETRACTED ARTICLE: Prognostic value of CD133 expression in cancer patients treated with chemoradiotherapy: a meta-analysis

Dynamic Tumor Growth Patterns in a Novel Murine Model of Colorectal Cancer

Overexpression of trefoil factor 3 (TFF3) contributes to the malignant progression in cervical cancer cells

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