Nuclear Receptor Interactions in Breast Cancer: The Role of Kinase Signaling Pathways

Despite global research efforts, breast cancer remains the leading cause of cancer death in women worldwide. The majority of these deaths are due to metastasis occurring years after the initial treatment of the primary tumor and occurs at a higher frequency in hormone receptor-positive (Estrogen and Progesterone; HR+) breast cancers. We have previously described the role of NUDT5 (Nudix-linked to moiety X-5) in HR+ breast cancer progression, specifically with regards to the growth of breast cancer stem cells (BCSCs). BCSCs are known to be the initiators of epithelial-to-mesenchyme transition (EMT), metastatic colonization, and growth. Therefore, a greater understanding of the proteins and signaling pathways involved in the metastatic process may open the door for therapeutic opportunities. In this review, we discuss the role of NUDT5 and other members of the NUDT family of enzymes in breast and other cancer types. We highlight the use of global omics data based on our recent phosphoproteomic analysis of progestin signaling pathways in breast cancer cells and how this experimental approach provides insight into novel crosstalk mechanisms for stratification and drug discovery projects aiming to treat patients with aggressive cancer.

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Mechanical strain regulates syndecan-4 expression and shedding in smooth muscle cells through differential activation of MAP kinase signaling pathways

AJP Cell Physiology ◽

10.1152/ajpcell.00093.2006 ◽

2007 ◽

Vol 292 (1) ◽

pp. C517-C525 ◽

Cited By ~ 14

Author(s):

Matheau A. Julien ◽

Peiyi Wang ◽

Carolyn A. Haller ◽

Jing Wen ◽

Elliot L. Chaikof

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Map Kinase ◽

Signaling Pathways ◽

Map Kinases ◽

Muscle Cells ◽

Kinase Signaling ◽

Fold Reduction ◽

Map Kinase Signaling

Syndecan-4 (S4) belongs to a family of transmembrane proteoglycans, acts as a coreceptor for growth factor binding as well as cell-matrix and cell-cell interactions, and is induced in neointimal smooth muscle cells (SMCs) after balloon catheter injury. We investigated S4 expression in SMCs in response to several force profiles and the role of MAP kinase signaling pathways in regulating these responses. S4 mRNA expression increased in response to 5% and 10% cyclic strain (4 h: 200 ± 34% and 182 ± 17%, respectively; P < 0.05) before returning to basal levels by 24 h. Notably, the SMC mechanosensor mechanism was reset after an initial 24-h “preconditioning” period, as evident by an increase in S4 gene expression following a change in cyclic stress from 10% to 20% (28 h: 181 ± 1%; P < 0.05). Mechanical stress induced a late decrease in cell-associated S4 protein levels (24 h: 70 ± 6%; P < 0.05), with an associated increase in S4 shedding (24 h: 537 ± 109%; P < 0.05). To examine the role of MAP kinases, cells were treated with U-0126 (ERK1/2 inhibitor), SB-203580 (p38 inhibitor), or JNKI I (JNK/SAPK inhibitor). Late reduction in cell-associated S4 levels was attributed to ERK1/2 and p38 signaling. In contrast, accelerated S4 shedding required both ERK1/2 (5-fold reduction in accelerated shedding; P < 0.05) and JNK/SAPK (4-fold reduction; P < 0.05) signaling. Given the varied functions of S4, stress-induced effects on SMC S4 expression and shedding may represent an additional component of the proinflammatory, growth-stimulating pathways that are activated in response to changes in the mechanical microenvironment of the vascular wall.

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Breast cancer: understanding etiology, addressing molecular signaling pathways, identifying therapeutic targets and strategizing the treatment

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v12i3.4779 ◽

2021 ◽

Vol 12 (3) ◽

pp. 1757-1769

Author(s):

Preeti Tanaji Mane ◽

Sangram Prakash Patil ◽

Balaji Sopanrao Wakure ◽

Pravin Shridhar Wakte

Keyword(s):

Breast Cancer ◽

Signaling Pathways ◽

Treatment Options ◽

Current Treatment ◽

Vital Role ◽

Molecular Signaling ◽

Breast Tumorigenesis ◽

Non Coding Rnas ◽

Cycle Regulation

Breast cancer has messed the life of a greater number of women being the most common cancer affecting them worldwide. A number of risk factors contribute the breast malignancy, however, genetic drift is accountable the most. Depending on the cell origin, invasiveness and receptors involved, breast cancer is classified into various subtypes. The accurate diagnosis of breast cancer is important as it defines the prognosis and directs the type of treatment required. A number of major signaling pathways involved in breast tumorigenesis and its development include estrogen receptors (ERs), HER2, Wnt/β-catenin, Notch, Hedgehog (Hh), PI3K and mTOR pathway. Furthermore, certain enzymes like Cyclin dependent kinases and breast tumor kinases also play a vital role in cell cycle regulation and therefore, in the development of breast neoplasms. Recent studies have also enlightened the role of non-coding RNAs in breast cancer development. This review discusses various aspects of breast cancer such as its etiology, subtypes, various signaling pathways involved, targets projected by these pathways and the current treatment options based on a few of these targets. Also, the role of different genes, enzymes and non-coding RNAs related to breast tumorigenesis and development is discussed.

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