Skip to main content
Top
Published in: Tumor Biology 12/2016

01-12-2016 | Original Article

FAT4 functions as a tumor suppressor in triple-negative breast cancer

Authors: Lingmi Hou, Maoshan Chen, Xiaobo Zhao, Jingdong Li, Shishan Deng, Jiani Hu, Hongwei Yang, Jun Jiang

Published in: Tumor Biology | Issue 12/2016

Login to get access

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is often associated with biologic behavior with frequent distant metastasis. FAT tumor suppressor homolog 4 (FAT4), a cadherin-related protein, is involved in a variety of biological processes as a tumor suppressor; however, the role of FAT4 in TNBC is still unclear. The aim of our study was to identify the role of FAT4 in TNBC and examine the underlying molecular mechanisms. The expression of FAT4 was evaluated by immunohistochemistry, western blotting, and qRT-PCR in a series of TNBC tissues. The effects of FAT4 on the ability of cell proliferation, migration, and invasion were assessed by MTT assay and migration and invasion assays. We demonstrated that the repression of FAT4 by shRNA could promote TNBC progression. Taken together, our findings provide evidence for a role of the FAT4 cluster as a tumor suppressor in TNBC patients and may serve as potential novel targets for the treatment of TNBC.
Literature
1.
go back to reference DeSantis C, Ma J, Bryan L, Jemal A. Breast cancer statistics, 2013. CA Cancer J Clin. 2014;64:52–62.CrossRefPubMed DeSantis C, Ma J, Bryan L, Jemal A. Breast cancer statistics, 2013. CA Cancer J Clin. 2014;64:52–62.CrossRefPubMed
2.
go back to reference Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747–52.CrossRefPubMed Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747–52.CrossRefPubMed
3.
go back to reference Fulford LG, Reis-Filho JS, Ryder K, Jones C, Gillett CE, Hanby A, Easton D, Lakhani SR. Basal-like grade III invasive ductal carcinoma of the breast: patterns of metastasis and long-term survival. Breast Cancer Res. 2007;9(1):R4.CrossRefPubMedPubMedCentral Fulford LG, Reis-Filho JS, Ryder K, Jones C, Gillett CE, Hanby A, Easton D, Lakhani SR. Basal-like grade III invasive ductal carcinoma of the breast: patterns of metastasis and long-term survival. Breast Cancer Res. 2007;9(1):R4.CrossRefPubMedPubMedCentral
4.
go back to reference Tomao F, Papa A, Zaccarelli E, Rossi L, Caruso D, Minozzi M, Vici P, Frati L, Tomao S. Triple-negative breast cancer: new perspectives for targeted therapies. Onco Targets Ther. 2015;8:177–93.CrossRefPubMedPubMedCentral Tomao F, Papa A, Zaccarelli E, Rossi L, Caruso D, Minozzi M, Vici P, Frati L, Tomao S. Triple-negative breast cancer: new perspectives for targeted therapies. Onco Targets Ther. 2015;8:177–93.CrossRefPubMedPubMedCentral
5.
go back to reference Cai J, Feng D, Hu L, Chen H, Yang G, Cai Q, Gao C, Wei D. FAT4 functions as a tumour suppressor in gastric cancer by modulating Wnt/beta-catenin signalling. Br J Cancer. 2015;113:1720–9.CrossRefPubMedPubMedCentral Cai J, Feng D, Hu L, Chen H, Yang G, Cai Q, Gao C, Wei D. FAT4 functions as a tumour suppressor in gastric cancer by modulating Wnt/beta-catenin signalling. Br J Cancer. 2015;113:1720–9.CrossRefPubMedPubMedCentral
6.
go back to reference Qi C, Zhu YT, Hu L, Zhu YJ. Identification of Fat4 as a candidate tumor suppressor gene in breast cancers. International journal of cancer Journal international du cancer. 2009;124:793–8.CrossRefPubMedPubMedCentral Qi C, Zhu YT, Hu L, Zhu YJ. Identification of Fat4 as a candidate tumor suppressor gene in breast cancers. International journal of cancer Journal international du cancer. 2009;124:793–8.CrossRefPubMedPubMedCentral
7.
go back to reference Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, Senn HJ. Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2011;22:1736–47.CrossRef Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, Senn HJ. Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2011;22:1736–47.CrossRef
8.
go back to reference Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med. 2010;363:1938–48.CrossRefPubMed Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med. 2010;363:1938–48.CrossRefPubMed
9.
go back to reference Thomas C, Strutt D. The roles of the cadherins fat and dachsous in planar polarity specification in Drosophila. Developmental dynamics: an official publication of the American Association of Anatomists. 2012;241:27–39.CrossRef Thomas C, Strutt D. The roles of the cadherins fat and dachsous in planar polarity specification in Drosophila. Developmental dynamics: an official publication of the American Association of Anatomists. 2012;241:27–39.CrossRef
10.
go back to reference Li M, Zhao H, Zhang X, Wood LD, Anders RA, Choti MA, Pawlik TM, Daniel HD, Kannangai R, Offerhaus GJ, Velculescu VE, Wang L, Zhou S, Vogelstein B, Hruban RH, Papadopoulos N, Cai J, Torbenson MS, Kinzler KW. Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma. Nat Genet. 2011;43:828–9.CrossRefPubMedPubMedCentral Li M, Zhao H, Zhang X, Wood LD, Anders RA, Choti MA, Pawlik TM, Daniel HD, Kannangai R, Offerhaus GJ, Velculescu VE, Wang L, Zhou S, Vogelstein B, Hruban RH, Papadopoulos N, Cai J, Torbenson MS, Kinzler KW. Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma. Nat Genet. 2011;43:828–9.CrossRefPubMedPubMedCentral
11.
go back to reference Yu J, Wu WK, Li X, He J, Li XX, Ng SS, Yu C, Gao Z, Yang J, Li M, Wang Q, Liang Q, Pan Y, Tong JH, To KF, Wong N, Zhang N, Chen J, Lu Y, Lai PB, Chan FK, Li Y, Kung HF, Yang H, Wang J, Sung JJ. Novel recurrently mutated genes and a prognostic mutation signature in colorectal cancer. Gut. 2015;64:636–45.CrossRefPubMed Yu J, Wu WK, Li X, He J, Li XX, Ng SS, Yu C, Gao Z, Yang J, Li M, Wang Q, Liang Q, Pan Y, Tong JH, To KF, Wong N, Zhang N, Chen J, Lu Y, Lai PB, Chan FK, Li Y, Kung HF, Yang H, Wang J, Sung JJ. Novel recurrently mutated genes and a prognostic mutation signature in colorectal cancer. Gut. 2015;64:636–45.CrossRefPubMed
12.
go back to reference Choi HJ, Park JH, Park M, Won HY, Joo HS, Lee CH, Lee JY, Kong G. UTX inhibits EMT-induced breast CSC properties by epigenetic repression of EMT genes in cooperation with LSD1 and HDAC1. EMBO Rep. 2015;16:1288–98.CrossRefPubMedPubMedCentral Choi HJ, Park JH, Park M, Won HY, Joo HS, Lee CH, Lee JY, Kong G. UTX inhibits EMT-induced breast CSC properties by epigenetic repression of EMT genes in cooperation with LSD1 and HDAC1. EMBO Rep. 2015;16:1288–98.CrossRefPubMedPubMedCentral
13.
go back to reference Ye X, Tam WL, Shibue T, Kaygusuz Y, Reinhardt F, Ng Eaton E, Weinberg RA. Distinct EMT programs control normal mammary stem cells and tumour-initiating cells. Nature. 2015;525:256–60.CrossRefPubMedPubMedCentral Ye X, Tam WL, Shibue T, Kaygusuz Y, Reinhardt F, Ng Eaton E, Weinberg RA. Distinct EMT programs control normal mammary stem cells and tumour-initiating cells. Nature. 2015;525:256–60.CrossRefPubMedPubMedCentral
14.
go back to reference Rhodes LV, Tate CR, Hoang VT, Burks HE, Gilliam D, Martin EC, Elliott S, Miller DB, Buechlein A, Rusch D, Tang H, Nephew KP, Burow ME, Collins-Burow BM. Regulation of triple-negative breast cancer cell metastasis by the tumor-suppressor liver kinase B1. Oncogenesis. 2015;4:e168.CrossRefPubMedPubMedCentral Rhodes LV, Tate CR, Hoang VT, Burks HE, Gilliam D, Martin EC, Elliott S, Miller DB, Buechlein A, Rusch D, Tang H, Nephew KP, Burow ME, Collins-Burow BM. Regulation of triple-negative breast cancer cell metastasis by the tumor-suppressor liver kinase B1. Oncogenesis. 2015;4:e168.CrossRefPubMedPubMedCentral
15.
go back to reference Li N, Xu H, Fan K, Liu X, Qi J, Zhao C, Yin P, Wang L, Li Z, Zha X. Altered beta1,6-GlcNAc branched N-glycans impair TGF-beta-mediated epithelial-to-mesenchymal transition through Smad signalling pathway in human lung cancer. J Cell Mol Med. 2014;18:1975–91.CrossRefPubMedPubMedCentral Li N, Xu H, Fan K, Liu X, Qi J, Zhao C, Yin P, Wang L, Li Z, Zha X. Altered beta1,6-GlcNAc branched N-glycans impair TGF-beta-mediated epithelial-to-mesenchymal transition through Smad signalling pathway in human lung cancer. J Cell Mol Med. 2014;18:1975–91.CrossRefPubMedPubMedCentral
16.
Metadata
Title
FAT4 functions as a tumor suppressor in triple-negative breast cancer
Authors
Lingmi Hou
Maoshan Chen
Xiaobo Zhao
Jingdong Li
Shishan Deng
Jiani Hu
Hongwei Yang
Jun Jiang
Publication date
01-12-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 12/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-5421-3

Other articles of this Issue 12/2016

Tumor Biology 12/2016 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine