Bone Metastatic Breast Cancer: Advances in Cell Signaling and Autophagy Related Mechanisms
Bone metastasis is a frequent complication of breast cancer with nearly 70% of metastatic breast cancer patients developing bone metastasis during the course of their disease. The bone represents a dynamic microenvironment which provides a fertile soil for disseminated tumor cells, however, the mech...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/17/4310 |
| _version_ | 1797521594855194624 |
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| author | Ahmad Othman Marcus Winogradzki Linus Lee Manish Tandon Alan Blank Jitesh Pratap |
| author_facet | Ahmad Othman Marcus Winogradzki Linus Lee Manish Tandon Alan Blank Jitesh Pratap |
| author_sort | Ahmad Othman |
| collection | DOAJ |
| description | Bone metastasis is a frequent complication of breast cancer with nearly 70% of metastatic breast cancer patients developing bone metastasis during the course of their disease. The bone represents a dynamic microenvironment which provides a fertile soil for disseminated tumor cells, however, the mechanisms which regulate the interactions between a metastatic tumor and the bone microenvironment remain poorly understood. Recent studies indicate that during the metastatic process a bidirectional relationship between metastatic tumor cells and the bone microenvironment begins to develop. Metastatic cells display aberrant expression of genes typically reserved for skeletal development and alter the activity of resident cells within the bone microenvironment to promote tumor development, resulting in the severe bone loss. While transcriptional regulation of the metastatic process has been well established, recent findings from our and other research groups highlight the role of the autophagy and secretory pathways in interactions between resident and tumor cells during bone metastatic tumor growth. These reports show high levels of autophagy-related markers, regulatory factors of the autophagy pathway, and autophagy-mediated secretion of matrix metalloproteinases (MMP’s), receptor activator of nuclear factor kappa B ligand (RANKL), parathyroid hormone related protein (PTHrP), as well as WNT5A in bone metastatic breast cancer cells. In this review, we discuss the recently elucidated mechanisms and their crosstalk with signaling pathways, and potential therapeutic targets for bone metastatic disease. |
| first_indexed | 2024-03-10T08:14:43Z |
| format | Article |
| id | doaj.art-8a24060cf5a74779bd346b5ca362af22 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T08:14:43Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-8a24060cf5a74779bd346b5ca362af222023-11-22T10:25:23ZengMDPI AGCancers2072-66942021-08-011317431010.3390/cancers13174310Bone Metastatic Breast Cancer: Advances in Cell Signaling and Autophagy Related MechanismsAhmad Othman0Marcus Winogradzki1Linus Lee2Manish Tandon3Alan Blank4Jitesh Pratap5Department of Anatomy & Cell Biology, Cell & Molecular Medicine, Rush University Medical Center, Chicago, IL 60612, USADepartment of Anatomy & Cell Biology, Cell & Molecular Medicine, Rush University Medical Center, Chicago, IL 60612, USADepartment of Anatomy & Cell Biology, Cell & Molecular Medicine, Rush University Medical Center, Chicago, IL 60612, USADepartment of Anatomy & Cell Biology, Cell & Molecular Medicine, Rush University Medical Center, Chicago, IL 60612, USADepartment of Anatomy & Cell Biology, Cell & Molecular Medicine, Rush University Medical Center, Chicago, IL 60612, USADepartment of Anatomy & Cell Biology, Cell & Molecular Medicine, Rush University Medical Center, Chicago, IL 60612, USABone metastasis is a frequent complication of breast cancer with nearly 70% of metastatic breast cancer patients developing bone metastasis during the course of their disease. The bone represents a dynamic microenvironment which provides a fertile soil for disseminated tumor cells, however, the mechanisms which regulate the interactions between a metastatic tumor and the bone microenvironment remain poorly understood. Recent studies indicate that during the metastatic process a bidirectional relationship between metastatic tumor cells and the bone microenvironment begins to develop. Metastatic cells display aberrant expression of genes typically reserved for skeletal development and alter the activity of resident cells within the bone microenvironment to promote tumor development, resulting in the severe bone loss. While transcriptional regulation of the metastatic process has been well established, recent findings from our and other research groups highlight the role of the autophagy and secretory pathways in interactions between resident and tumor cells during bone metastatic tumor growth. These reports show high levels of autophagy-related markers, regulatory factors of the autophagy pathway, and autophagy-mediated secretion of matrix metalloproteinases (MMP’s), receptor activator of nuclear factor kappa B ligand (RANKL), parathyroid hormone related protein (PTHrP), as well as WNT5A in bone metastatic breast cancer cells. In this review, we discuss the recently elucidated mechanisms and their crosstalk with signaling pathways, and potential therapeutic targets for bone metastatic disease.https://www.mdpi.com/2072-6694/13/17/4310breast cancerbone metastasiscell signalingautophagytumor-derived factorsmicroenvironment-derived factors |
| spellingShingle | Ahmad Othman Marcus Winogradzki Linus Lee Manish Tandon Alan Blank Jitesh Pratap Bone Metastatic Breast Cancer: Advances in Cell Signaling and Autophagy Related Mechanisms Cancers breast cancer bone metastasis cell signaling autophagy tumor-derived factors microenvironment-derived factors |
| title | Bone Metastatic Breast Cancer: Advances in Cell Signaling and Autophagy Related Mechanisms |
| title_full | Bone Metastatic Breast Cancer: Advances in Cell Signaling and Autophagy Related Mechanisms |
| title_fullStr | Bone Metastatic Breast Cancer: Advances in Cell Signaling and Autophagy Related Mechanisms |
| title_full_unstemmed | Bone Metastatic Breast Cancer: Advances in Cell Signaling and Autophagy Related Mechanisms |
| title_short | Bone Metastatic Breast Cancer: Advances in Cell Signaling and Autophagy Related Mechanisms |
| title_sort | bone metastatic breast cancer advances in cell signaling and autophagy related mechanisms |
| topic | breast cancer bone metastasis cell signaling autophagy tumor-derived factors microenvironment-derived factors |
| url | https://www.mdpi.com/2072-6694/13/17/4310 |
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