In many cancer, ALDH1A1 found to be associated with chemoresistance. Does anyone has comprehensive understanding on the molecular mechanism of ALDH1A1 mediated chemoresistance? I just found an article showing ABCB1 modulation through ALDH1A1-NEK2 pathway. Are there any more gene/protein that directly linked with ABC transporters as well as ALDH1A1? Any suggestion will be appreciable.
There are three isoforms of aldehyde dehydrogenases (ALDH), one of which is highly expressed in cancer stem cells (CSCs). That is why Aldefluor assay is useful to purify the CSC population especially in CD44(high)/CD24(low) fraction. ALDH is expressed in the normal liver and responsible for the oxidation of aldehydes to carboxylic acids. This anti-toxic effect refｌects the capacity of the resistance to cytotoxic anti-cancer drugs.
ALDH1 expression is found in highly plastic epigenetically heterogeneous cell lines, containing morphologically distiinct epithelial and mesenchymal cell types. Since it is known that heterogeneity corresponds to resistance to chemotherapy these distinct cell types in ALDH1 expressing cell lines are cooperating with a sheer innumerous number of synergistic interactions. To delineate which interaction of exactly ALDH1 with other proteins may be CAUSATIVE for chemoresistance should be looked at in the context of all the other synergistic interactions that are correlating with expression of ALDH (and that is many). Good luck.
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