Abstract
Understanding mechanisms of cancer development is mandatory for disease prevention and management. In healthy tissue, the microenvironment or niche governs stem cell fate by regulating the availability of soluble molecules, cell-cell contacts, cell-matrix interactions, and physical constraints. Gaining insight into the biology of the stem cell microenvironment is of utmost importance, since it plays a role at all stages of tumorigenesis, from (stem) cell transformation to tumor escape. In this context, BMPs (Bone Morphogenetic Proteins), are key mediators of stem cell regulation in both embryonic and adult organs such as hematopoietic, neural and epithelial tissues. BMPs directly regulate the niche and stem cells residing within. Among them, BMP2 and BMP4 emerged as master regulators of normal and tumorigenic processes. Recently, a number of studies unraveled important mechanisms that sustain cell transformation related to dysregulations of the BMP pathway in stem cells and their niche (including exposure to pollutants such as bisphenols). Furthermore, a direct link between BMP2/BMP4 binding to BMP type 1 receptors and the emergence and expansion of cancer stem cells was unveiled. In addition, a chronic exposure of normal stem cells to abnormal BMP signals contributes to the emergence of cancer stem cells, or to disease progression independently of the initial transforming event. In this review, we will illustrate how the regulation of stem cells and their microenvironment becomes dysfunctional in cancer via the hijacking of BMP signaling with main examples in myeloid leukemia and breast cancers.
Highlights
Cancer is a major public health issue considering its high mortality rate, increasing incidence, and cost to society
Treatment-induced quiescence of residual cancer stem cell (CSC) relies on the activation of Jak2-Stat3 signaling, mediated by BMP4 released from surrounding mesenchymal cells (Jeanpierre et al, 2021)
Abnormalities of BMP signaling are reported in many cancers, with studies mainly focusing on advanced stages while its roles in early transforming events are emerging
Summary
Cancer is a major public health issue considering its high mortality rate, increasing incidence, and cost to society. Immature epithelial cells (SCs and progenitors) express different elements of the BMP pathway, indicating that BMPs could play a role in normal SC regulation. Abnormal BMP2 production by SCs microenvironment together with BMP2-driven alterations of epithelial SC fate are involved in the emergence of luminal breast cancer cells (Chapellier et al, 2015).
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