Altered BMP2/4 Signaling in Stem Cells and Their Niche: Different Cancers but Similar Mechanisms, the Example of Myeloid Leukemia and Breast Cancer

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.

Bioinformatics Method Was Used to Analyze the Highly Expressed Gene FAM83A of Breast Cancer in Young Women

“…The mammary gland is the organ that most often develops benign and malignant tumors, and cancerous hyperplasia is fundamentally different from benign tumors, and the treatment plan is completely different. Therefore, when selecting high expression genes for breast cancer, clinicians hope to look for genes that are highly expressed in cancer tissues and are not expressed or low expression in benign tumor tissues, which are more valuable for helping clinical diagnosis and treatment [ 40 ]. The CGAP SAGE database can analyze tumor tissue gene expression profiles and look for tumor-specific expression of new genes in the SAGE library.…”

High glucose promotes the progression of colorectal cancer by activating the BMP4 signaling and inhibited by glucagon-like peptide-1 receptor agonist

“…BMP4 is increased in patients with metabolic disorders such as DM, obesity, and nonalcoholic fatty liver disease(NAFLD), and its level is negatively associated with insulin sensitivity [ 22 , 50 ]. Besides, the upregulated BMP4 also has been reported to be associated with many cancers and negatively associated with overall survival [ 51 , 52 ]. The aberrant activation of the Wnt/β-catenin pathway could increase the expression of BMP4, facilitating the invasiveness and tumorigenesis of CRC [ 15 ].…”

Cancer Bioenergetics and Tumor Microenvironments—Enhancing Chemotherapeutics and Targeting Resistant Niches through Nanosystems

“…Emerging studies elucidate that CSC or CIS are the major mechanisms of chemotherapeutic resistance in cancers, including colorectal, breast, bone, brain, etc. [79][80][81]. The CSC resides within a distinct microenvironments within the tumor, the CSC niche [82].…”