Expression of BMP-4 in papillary thyroid carcinoma and its correlation with tumor invasion and progression

Meng, Xia; Zhu, Peng; Li, Ning; Hu, Jinchen; Wang, Shaoguang; Pang, Shuguang; Wang, Jiahui

doi:10.1016/j.prp.2017.01.008

Cited by 13 publications

(8 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, with CML progression towards more advanced phases and the acquisition of resistance to treatment, the BMP4 signal becomes predominant 38 . This suggests that the BMP4 signal is related to more aggressive or advanced disease as identified in cancers of other origins such as liver (HCC) 39 , thyroid (PTC) 40 and bladder 41 . In malignant glioma, while BMP4 appears to induce differentiation of glioma cancer stem-like cells 42 , 43 , an epigenetic repression of the BMPR1B receptors contributes to the CSC phenotype in these tumors 10 .…”

Section: Discussionmentioning

confidence: 99%

A new signaling cascade linking BMP4, BMPR1A, ΔNp73 and NANOG impacts on stem-like human cell properties and patient outcome

Voeltzel¹,

Flores-Violante²,

Zylbersztejn³

et al. 2018

Cell Death Dis

View full text Add to dashboard Cite

In a significant number of cases cancer therapy is followed by a resurgence of more aggressive tumors derived from immature cells. One example is acute myeloid leukemia (AML), where an accumulation of immature cells is responsible for relapse following treatment. We previously demonstrated in chronic myeloid leukemia that the bone morphogenetic proteins (BMP) pathway is involved in stem cell fate and contributes to transformation, expansion, and persistence of leukemic stem cells. Here, we have identified intrinsic and extrinsic dysregulations of the BMP pathway in AML patients at diagnosis. BMP2 and BMP4 protein concentrations are elevated within patients’ bone marrow with a BMP4-dominant availability. This overproduction likely depends on the bone marrow microenvironment, since MNCs do not overexpress BMP4 transcripts. Intrinsically, the receptor BMPR1A transcript is increased in leukemic samples with more cells presenting this receptor at the membrane. This high expression of BMPR1A is further increased upon BMP4 exposure, specifically in AML cells. Downstream analysis demonstrated that BMP4 controls the expression of the survival factor ΔNp73 through its binding to BMPR1A. At the functional level, this results in the direct induction of NANOG expression and an increase of stem-like features in leukemic cells, as shown by ALDH and functional assays. In addition, we identified for the first time a strong correlation between ΔNp73, BMPR1A and NANOG expression with patient outcome. These results highlight a new signaling cascade initiated by tumor environment alterations leading to stem-cell features and poor patients’ outcome.

show abstract

Section: Discussionmentioning

confidence: 99%

A new signaling cascade linking BMP4, BMPR1A, ΔNp73 and NANOG impacts on stem-like human cell properties and patient outcome

Voeltzel¹,

Flores-Violante²,

Zylbersztejn³

et al. 2018

Cell Death Dis

View full text Add to dashboard Cite

show abstract

“…In addition, BMP signaling has also been directly implicated in thyroid-lineage specification [95,96] as well as in thyroid carcinoma [97]. Of note, thyroid hormone status interferes with estrogen target gene expression in breast cancer samples in menopausal women [98].…”

Section: Early Events Of Breast Carcinogenesismentioning

confidence: 99%

Early Steps of Mammary Stem Cell Transformation by Exogenous Signals; Effects of Bisphenol Endocrine Disrupting Chemicals and Bone Morphogenetic Proteins

Jung

Maguer-Satta

Guyot

2019

Cancers

View full text Add to dashboard Cite

Estrogens are major regulators of the mammary gland development, notably during puberty, via estrogen receptor (ER) activation, leading to the proliferation and differentiation of mammary cells. In addition to estrogens, the bone morphogenetic proteins (BMPs) family is involved in breast stem cell/progenitor commitment. However, these two pathways that synergistically contribute to the biology of the normal mammary gland have also been described to initiate and/or promote breast cancer development. In addition to intrinsic events, lifestyle habits and exposure to environmental cues are key risk factors for cancer in general, and especially for breast cancer. In the latter case, bisphenol A (BPA), an estrogen-mimetic compound, is a critical pollutant both in terms of the quantities released in our environment and of its known and speculated effects on mammary gland biology. In this review, we summarize the current knowledge on the actions of BMPs and estrogens in both normal mammary gland development and breast cancer initiation, dissemination, and resistance to treatment, focusing on the dysregulations of these processes by BPA but also by other bisphenols, including BPS and BPF, initially considered as safer alternatives to BPA.

show abstract

“…In this study, BMP4/7 exhibited stronger ability to control systemic hepcidin synthesis in TC than did IL-6. Similarly, it was reported that BMP4 expression is involved in crucial biological events in tumors, such as invasion 29 . Therefore, the BMP-antagonist SOSTDC1 can control hepcidin synthesis in TC.…”

Section: Discussionmentioning

confidence: 88%

E4BP4 promotes thyroid cancer proliferation by modulating iron homeostasis through repression of hepcidin

et al. 2018

View full text Add to dashboard Cite

Iron homeostasis is critical to mammals, and dysregulation in iron homeostasis usually leads to severe disorders including various cancers. Massive hepcidin secretion is an indicator of thyroid cancer, but the molecular mechanisms responsible for this dysregulation are unknown. Hepcidin secretion from thyroid cancer cells also leads to decreased expression of the iron exporter, ferroportin (FPN), and increased intracellular iron retention, which promote cancer proliferation. In this study, we examined the role of hepcidin in thyroid cancer (TC) and the molecular bases of its signaling. Synthesis of hepcidin is regulated by the BMP4/7 agonist SOSTDC1, which was downregulated in TC; SOSTDC1 downregulation was correlated with G9a-mediated hypermethylation in its promoter. The binding of G9a to the SOSTDC1 promoter requires E4BP4, which interacts with G9a to form a multi-molecular complex that contributes to SOSTDC1 silencing. Silencing of E4BP4 or G9a has similar effects to SOSTDC1 overexpression, which suppresses secretion of hepcidin and inhibits TC cell proliferation. Furthermore, our in vivo xenograft data indicated that depletion of E4BP4 also inhibits cancer growth, reduces hepcidin secretion, and reduces G9a nuclear transportation. Iron homeostasis and tumor growth in TC may be regulated by an E4BP4-dependent epigenetic mechanism. These findings suggest a new mechanism of cellular iron dysfunction through the E4BP4/G9a/SOSTDC1/hepcidin pathway, which is an essential link in TC.

show abstract

Expression of BMP-4 in papillary thyroid carcinoma and its correlation with tumor invasion and progression

Cited by 13 publications

References 27 publications

A new signaling cascade linking BMP4, BMPR1A, ΔNp73 and NANOG impacts on stem-like human cell properties and patient outcome

A new signaling cascade linking BMP4, BMPR1A, ΔNp73 and NANOG impacts on stem-like human cell properties and patient outcome

Early Steps of Mammary Stem Cell Transformation by Exogenous Signals; Effects of Bisphenol Endocrine Disrupting Chemicals and Bone Morphogenetic Proteins

E4BP4 promotes thyroid cancer proliferation by modulating iron homeostasis through repression of hepcidin

Contact Info

Product

Resources

About