11P - Glycolysis enzyme screenings identify non-glycolytic function of aldolase A that interacts and alters F-actin dynamics to promote lung cancer metastasis
- Yu-Chan Chang (TW)
- Michael Hsiao (TW)
- Yu-Chan Chang (TW)
Abstract
Background
In recent years, cancer metastasis remains a serious issue for drug development and target therapy. Although the metabolic reprogramming including glycolysis appears to promote cancer metastasis, the molecular mechanism by which this occurs remains unclear.
Methods
From high throughput screening of glycolytic enzymes, we investigated aldolase A (ALDOA) as the most significant enzyme promoting cell metastasis in vitro and in vivo. Furthermore, we recruited the enzyme inhibitors and enzyme-dead constructs to compromised function of aldolase A.
Results
We established a His-tagged ALDOA construct model and found ALDOA directed protein-protein interaction (PPI) with g-actin and the status correlated with malignant cancer cells, whereas in normal cell it did not. Meta-analysis of intergraded RNA and protein levels suggested ALDOA could be a prognostic marker in several cancer types. Moreover, compared with non-tumor tissues increased levels of ALDOA and g-actin are commonly detected in malignancies and strongly predict a worse prognosis in cancer patients. Therefore, we designed a specific peptide to block the interaction between ALDOA and g-actin to decrease the metastatic ability of cancer cells in vitro and prolong survival rate in vivo.
Conclusions
These findings suggest a new therapeutic strategy for targeting the cancer-associated PPI between ALDOA and g-actin to combat metastatic cancers.
Legal entity responsible for the study
Genomics Research Center, Academia Sinica, Taiwan
Funding
Has not received any funding
Disclosure
All authors have declared no conflicts of interest.
