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ABSTRACT: Background
Meta-analysis shows that women with diabetes have a 20% increased risk of breast cancer and also an increased risk for distant metastasis and mortality. The molecular mechanisms for distant metastasis and mortality in breast cancer patients with diabetes are not very well understood.Methods
We compared the effect of physiological (5?mM) and diabetic (10?mM) levels of glucose on malignant breast epithelial cell invasion and stemness capabilities. We performed microRNA array to determine the dysregulated microRNAs in hyperglycaemic conditions and performed functional and molecular analysis of the gene targets.Results
Hyperglycaemia leads to hyperactivation of cancer stem cell pool and enhances invasive ability of breast cancer cells. MiR-424 seems to be a key regulator of cancer cell stemness and invasion. Knockdown of miR-424 in cancer cells under euglycaemic conditions leads to enhanced invasion and stem cell activity, whereas ectopic expression of miR-424 in cancer cells under hyperglycaemic conditions results in suppressed invasion and stem cell activity. Cdc42, a target of miR-424, influences cancer stem cell activity by positively regulating prdm14 through activation of pak1 (p-21-activated kinase 1) and stat5.Conclusions
Our findings establish miR-424??cdc42??prdm14 axis as a key molecular signalling cascade that might influence breast cancer progression in diabetic patients through hyperactivation of cancer stem cells.
SUBMITTER: Nandy SB
PROVIDER: S-EPMC5729435 | biostudies-literature | 2017 Nov
REPOSITORIES: biostudies-literature
Nandy Sushmita Bose SB Orozco Alexis A Lopez-Valdez Rebecca R Roberts Rene R Subramani Ramadevi R Arumugam Arunkumar A Dwivedi Alok Kumar AK Stewart Viktoria V Prabhakar Gautham G Jones Stephanie S Lakshmanaswamy Rajkumar R
British journal of cancer 20171012 11
<h4>Background</h4>Meta-analysis shows that women with diabetes have a 20% increased risk of breast cancer and also an increased risk for distant metastasis and mortality. The molecular mechanisms for distant metastasis and mortality in breast cancer patients with diabetes are not very well understood.<h4>Methods</h4>We compared the effect of physiological (5 mM) and diabetic (10 mM) levels of glucose on malignant breast epithelial cell invasion and stemness capabilities. We performed microRNA a ...[more]