Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
Add more filters










Database
Language
Publication year range
1.
J Mol Endocrinol ; 70(3)2023 04 01.
Article in English | MEDLINE | ID: mdl-36629385

ABSTRACT

The tumor microenvironment is a dynamic ecosystem of stromal and immune cells that, under the influence of cancer cells, govern biochemical signaling, mechanical signaling via production and remodeling of the extracellular matrix (ECM), formation of vascular networks, and ultimately promotion of tumor growth. In breast cancer, hormone receptor-mediated signaling is a key coordinator of cancer cell proliferation and invasiveness not only through cell-autonomous means but also via cancer cell-stroma cross-talk. In the absence of hormone receptors, a different microenvironment landscape emerges, which comes with its own challenges for therapy. This review summarizes the current knowledge regarding the associations of hormone receptor profiles with composition of the microenvironment, how hormones directly influence stromal cells, immune cells and cells associated with the vasculature, and the paracrine mechanisms that lead to the formation of a tumor-promoting ECM.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/pathology , Tumor Microenvironment/physiology , Ecosystem , Neoplasm Invasiveness/pathology , Extracellular Matrix/pathology , Hormones
2.
Adv Exp Med Biol ; 1329: 399-417, 2021.
Article in English | MEDLINE | ID: mdl-34664249

ABSTRACT

It is becoming increasingly appreciated that biophysical influences on tissues are at least as important as biochemical influences in regulating normal development and homeostasis. Furthermore, diseases of aberrant tissue homeostasis such as cancers are driven by the abnormal biophysics of cancerous tissues. The mammary gland, a mechanoresponsive tissue, is exquisitely sensitive to changes in its mechanical microenvironment. Forces play an important role in normal mammary development, lactation, and involution, as well as in mammary neoplasia. As such the mechanical influences on normal tissue homeostasis and neoplasia are easily studied in this tissue. Here, we discuss the role of mechanical forces in these developmental and homeostatic processes and highlight insights gained from new findings in the field of mammary mechanobiology. We also discuss the potential for harnessing these insights into novel anticancer therapy approaches that halt tumor progression, with opportunities to revolutionize cancer care and outcomes for patients.


Subject(s)
Breast Neoplasms , Mammary Neoplasms, Animal , Animals , Female , Homeostasis , Humans , Lactation , Mechanotransduction, Cellular , Tumor Microenvironment
4.
Nat Cell Biol ; 22(7): 882-895, 2020 07.
Article in English | MEDLINE | ID: mdl-32451439

ABSTRACT

It is well accepted that cancers co-opt the microenvironment for their growth. However, the molecular mechanisms that underlie cancer-microenvironment interactions are still poorly defined. Here, we show that Rho-associated kinase (ROCK) in the mammary tumour epithelium selectively actuates protein-kinase-R-like endoplasmic reticulum kinase (PERK), causing the recruitment and persistent education of tumour-promoting cancer-associated fibroblasts (CAFs), which are part of the cancer microenvironment. An analysis of tumours from patients and mice reveals that cysteine-rich with EGF-like domains 2 (CRELD2) is the paracrine factor that underlies PERK-mediated CAF education downstream of ROCK. We find that CRELD2 is regulated by PERK-regulated ATF4, and depleting CRELD2 suppressed tumour progression, demonstrating that the paracrine ROCK-PERK-ATF4-CRELD2 axis promotes the progression of breast cancer, with implications for cancer therapy.


Subject(s)
Breast Neoplasms/pathology , Cancer-Associated Fibroblasts/pathology , Cell Adhesion Molecules/metabolism , Cellular Reprogramming , Extracellular Matrix Proteins/metabolism , eIF-2 Kinase/metabolism , rho-Associated Kinases/metabolism , Activating Transcription Factor 4/genetics , Activating Transcription Factor 4/metabolism , Animals , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Cancer-Associated Fibroblasts/metabolism , Cell Adhesion Molecules/genetics , Cells, Cultured , Disease Models, Animal , Endoplasmic Reticulum/metabolism , Extracellular Matrix Proteins/genetics , Female , Humans , Mice , Paracrine Communication , eIF-2 Kinase/genetics , rho-Associated Kinases/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...