A novel cross-communication of HIF-1α and HIF-2α with Wnt signaling in TNBC and influence of hypoxic microenvironment in the formation of an organ-on-chip model of breast cancer

Abstract

The microenvironment role is very important in cancer development. The epithelial-mesenchymal transition of the cancer cells depends upon specific signaling and microenvironmental conditions, such as hypoxic conditions. The crosstalk between hypoxia and Wnt signaling through some molecular mechanism in TNBC is related. Cross-communication between hypoxia and Wnt signaling in cancer cells is known, but the detailed mechanism in TNBC is unknown. This review includes the role of the hypoxia microenvironment in TNBC and the novel crosstalk of the Wnt signaling and hypoxia. When targeted, the new pathway and crosstalk link may be a solution for metastatic TNBC and chemoresistance. The microenvironment influences cancer's metastasis, which changes from person to person. Therefore, organ-on-a-chip is a very novel model to test the drugs clinically before going for human trials, focusing on personalized medications can be done. The effect of the hypoxia microenvironment on breast cancer stem cells is still unknown. Apart from all the published papers, this paper mainly focuses only on the hypoxic microenvironment and its association with the growth of TNBC. The medicines or small proteins, drugs, mimics, and inhibitors targeting wnt and hypoxia genes are consolidated in this review paper.

Keywords: Hypoxia; Microenvironment; Organ-on-chip; Triple-negative breast cancer; Wnt signaling.