Aldolase B Overexpression is Associated with Poor Prognosis and Promotes Tumor Progression by Epithelial-Mesenchymal Transition in Colorectal Adenocarcinoma.

Abstract

BACKGROUND:

Glycolysis is considered to be the root of cancer development and progression, which involved a multi-step enzymatic reaction. Our study aimed at figuring out which glycolysis enzyme participates in the development of colorectal cancer and its possible mechanisms.

METHODS:

We firstly screened out Aldolase B (ALDOB) by performing qRT-PCR arrays of glycolysis-related genes in five paired liver metastasis and primary colorectal tissues, and further detected ALDOB protein with immunohistochemistry in tissue microarray (TMA) consisting of 229 samples from stage I-III colorectal cancer patients. CRISPR-Cas9 method was adopted to create knock out colon cancer cell lines (LoVo and SW480) of ALDOB. The effect of ALDOB on cell proliferation and metastasis was examined in vitro using colony formation assay as well as transwell migration and invasion assay, respectively.

RESULTS:

In TMA, there was 64.6% of samples demonstrated strong intensity of ALDOB. High ALDOB expression were associated with poor overall survival and disease-free survival in both univariate and multivariate regression analyses (P<0.05). In vitro functional studies of CCK-8 demonstrated that silencing ALDOB expression significantly (P<0.05) inhibited proliferation, migration and invasion of colon cancer cells. Mechanically, silencing ALDOB activated epithelial markers and repressed mesenchymal markers, indicating inactivation of ALDOB may lead to inhibition of epithelial-mesenchymal transition (EMT).

CONCLUSION:

Upregulation of ALDOB promotes colorectal cancer metastasis by facilitating EMT and acts as a potential prognostic factor and therapeutic target in colorectal cancer.

• Authors: Qingguo Li, Yaqi Li, Junyan Xu, Sheng Wang, Ye Xu, Xinxiang Li, Sanjun Cai
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 42 Issue 1 Pg. 397-406 ( 2017) ISSN: 1421-9778 [Electronic] Germany
• PMID: 28558381 (Publication Type: Journal Article)
• Copyright: © 2017 The Author(s). Published by S. Karger AG, Basel.

Chemical References

• Vimentin
• Fructose-Bisphosphate Aldolase

Topics

• Adenocarcinoma (diagnosis, mortality, pathology)
• Aged
• CRISPR-Cas Systems (genetics)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Colorectal Neoplasms (diagnosis, mortality, pathology)
• Disease-Free Survival
• Epithelial-Mesenchymal Transition
• Female
• Fructose-Bisphosphate Aldolase (antagonists & inhibitors, genetics, metabolism)
• Glycolysis
• Humans
• Liver Neoplasms (pathology, secondary)
• Male
• Middle Aged
• Neoplasm Staging
• Prognosis
• RNA Interference
• Vimentin (metabolism)