Downregulation of Delta-aminolevulinate Dehydratase is Associated with Poor Prognosis In patients with Breast Cancer

Overview

Journal Cancer Sci

Specialty Oncology

Date 2017 Apr 14

PMID 28403546

Citations 8

Authors

Jie Ge

Yue Yu

Fei Xin

Zheng-Jun Yang

Hong-Meng Zhao

Xin Wang

Zhong-Sheng Tong

Xu-Chen Cao

Affiliations

Soon will be listed here.

Abstract

Delta-aminolevulinate dehydratase (ALAD) catalyzes the second step in the biosynthesis of heme and is also an endogenous inhibitor of the 26S proteasome. The role of ALAD in breast cancer progression is still unclear. In this study, we found that the expression of ALAD was downregulated in breast cancer tissues compared with adjacent normal breast tissues. Enhanced ALAD expression was associated with a favorable outcome in patients with breast cancer. Overexpression of ALAD suppresses breast cancer cell proliferation and invasion and inhibits the epithelial-mesenchymal transition phenotype. Furthermore, we found that ALAD regulates transforming growth factor-β-mediated breast cancer progression. This finding suggests that ALAD might be a potential biomarker for breast cancer that suppresses breast cancer progression by regulating transforming growth factor-β-mediated epithelial-mesenchymal transition.

Citing Articles

A four-gene signature predicts overall survival of patients with esophageal adenocarcinoma.

Mao Y, Zhang H, He X, Chen J, Xi L, Chen Y Transl Cancer Res. 2024; 13(3):1382-1393.

PMID: 38617513 PMC: 11009802. DOI: 10.21037/tcr-23-1798.

Systematic proteome-wide Mendelian randomization using the human plasma proteome to identify therapeutic targets for lung adenocarcinoma.

Zhang L, Xiong Y, Zhang J, Feng Y, Xu A J Transl Med. 2024; 22(1):330.

PMID: 38576019 PMC: 10993587. DOI: 10.1186/s12967-024-04919-z.

Characterization of cancer-associated fibroblasts (CAFs) and development of a CAF-based risk model for triple-negative breast cancer.

Wang G, Zhang H, Shen X, Jin W, Wang X, Zhou Z Cancer Cell Int. 2023; 23(1):294.

PMID: 38007443 PMC: 10676599. DOI: 10.1186/s12935-023-03152-w.

Metabolic genes, a potential predictor of prognosis and immunogenicity of clear cell renal cell carcinoma.

Ji C, Wei X, Yao L, Wang Y, Cong R, Song N Am J Cancer Res. 2023; 13(4):1387-1406.

PMID: 37168330 PMC: 10164820.

A Recap of Heme Metabolism towards Understanding Protoporphyrin IX Selectivity in Cancer Cells.

Kiening M, Lange N Int J Mol Sci. 2022; 23(14).

PMID: 35887311 PMC: 9324066. DOI: 10.3390/ijms23147974.

References

Mani S, Guo W, Liao M, Eaton E, Ayyanan A, Zhou A . The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008; 133(4):704-15. PMC: 2728032. DOI: 10.1016/j.cell.2008.03.027. View

van Bemmel D, Boffetta P, Liao L, Berndt S, Menashe I, Yeager M . Comprehensive analysis of 5-aminolevulinic acid dehydrogenase (ALAD) variants and renal cell carcinoma risk among individuals exposed to lead. PLoS One. 2011; 6(7):e20432. PMC: 3140467. DOI: 10.1371/journal.pone.0020432. View

Song J . EMT or apoptosis: a decision for TGF-beta. Cell Res. 2007; 17(4):289-90. DOI: 10.1038/cr.2007.25. View

Scheel C, Weinberg R . Cancer stem cells and epithelial-mesenchymal transition: concepts and molecular links. Semin Cancer Biol. 2012; 22(5-6):396-403. PMC: 6220425. DOI: 10.1016/j.semcancer.2012.04.001. View

Chen W, Zheng R, Zhang S, Zhao P, Li G, Wu L . The incidences and mortalities of major cancers in China, 2009. Chin J Cancer. 2013; 32(3):106-12. PMC: 3845591. DOI: 10.5732/cjc.013.10018. View

Taylor M, Parvani J, Schiemann W . The pathophysiology of epithelial-mesenchymal transition induced by transforming growth factor-beta in normal and malignant mammary epithelial cells. J Mammary Gland Biol Neoplasia. 2010; 15(2):169-90. PMC: 3721368. DOI: 10.1007/s10911-010-9181-1. View

Neslund-Dudas C, Levin A, Rundle A, Beebe-Dimmer J, Bock C, Nock N . Case-only gene-environment interaction between ALAD tagSNPs and occupational lead exposure in prostate cancer. Prostate. 2014; 74(6):637-46. PMC: 4112406. DOI: 10.1002/pros.22781. View

Rousseau M, Parent M, Nadon L, Latreille B, Siemiatycki J . Occupational exposure to lead compounds and risk of cancer among men: a population-based case-control study. Am J Epidemiol. 2007; 166(9):1005-14. DOI: 10.1093/aje/kwm183. View

Ge J, Yu Y, Xin F, Yang Z, Zhao H, Wang X . Downregulation of delta-aminolevulinate dehydratase is associated with poor prognosis in patients with breast cancer. Cancer Sci. 2017; 108(4):604-611. PMC: 5406535. DOI: 10.1111/cas.13180. View

10.

Katsuno Y, Lamouille S, Derynck R . TGF-β signaling and epithelial-mesenchymal transition in cancer progression. Curr Opin Oncol. 2012; 25(1):76-84. DOI: 10.1097/CCO.0b013e32835b6371. View

11.

Tian Y, Yu Y, Hou L, Chi J, Mao J, Xia L . Serum deprivation response inhibits breast cancer progression by blocking transforming growth factor-β signaling. Cancer Sci. 2016; 107(3):274-80. PMC: 4814251. DOI: 10.1111/cas.12879. View

12.

Parvani J, Taylor M, Schiemann W . Noncanonical TGF-β signaling during mammary tumorigenesis. J Mammary Gland Biol Neoplasia. 2011; 16(2):127-46. PMC: 3723114. DOI: 10.1007/s10911-011-9207-3. View

13.

Heldin C, Landstrom M, Moustakas A . Mechanism of TGF-beta signaling to growth arrest, apoptosis, and epithelial-mesenchymal transition. Curr Opin Cell Biol. 2009; 21(2):166-76. DOI: 10.1016/j.ceb.2009.01.021. View

14.

Yu Y, Zhao Y, Sun X, Ge J, Zhang B, Wang X . Down-regulation of miR-129-5p via the Twist1-Snail feedback loop stimulates the epithelial-mesenchymal transition and is associated with poor prognosis in breast cancer. Oncotarget. 2015; 6(33):34423-36. PMC: 4741463. DOI: 10.18632/oncotarget.5406. View

15.

Heldin C, Vanlandewijck M, Moustakas A . Regulation of EMT by TGFβ in cancer. FEBS Lett. 2012; 586(14):1959-70. DOI: 10.1016/j.febslet.2012.02.037. View

16.

Bhatti P, Stewart P, Linet M, Blair A, Inskip P, Rajaraman P . Comparison of occupational exposure assessment methods in a case-control study of lead, genetic susceptibility and risk of adult brain tumours. Occup Environ Med. 2010; 68(1):4-9. PMC: 3828743. DOI: 10.1136/oem.2009.048132. View

17.

Li J, Liu S, Zhou H, Qu L, Yang J . starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 2013; 42(Database issue):D92-7. PMC: 3964941. DOI: 10.1093/nar/gkt1248. View

18.

Padua D, Massague J . Roles of TGFbeta in metastasis. Cell Res. 2008; 19(1):89-102. DOI: 10.1038/cr.2008.316. View

19.

Shang Z, Cai Q, Zhang M, Zhu S, Ma Y, Sun L . A switch from CD44⁺ cell to EMT cell drives the metastasis of prostate cancer. Oncotarget. 2014; 6(2):1202-16. PMC: 4359227. DOI: 10.18632/oncotarget.2841. View

20.

Tian M, Schiemann W . The TGF-beta paradox in human cancer: an update. Future Oncol. 2009; 5(2):259-71. PMC: 2710615. DOI: 10.2217/14796694.5.2.259. View