scholarly journals Bone Metastatic Breast Cancer: Advances in Cell Signaling and Autophagy Related Mechanisms

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4310
Author(s):  
Ahmad Othman ◽  
Marcus Winogradzki ◽  
Linus Lee ◽  
Manish Tandon ◽  
Alan Blank ◽  
...  

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.


2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that the receptor for chemokines XCL1 and XCL2, the X-C motif chemokine receptor 1, encoded by XCR1, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast (4). XCR1 was also differentially expressed in the tumor cells of patients with triple negative breast cancer (5). XCR1 mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of XCR1 in primary tumors was significantly correlated with patient recurrence-free survival. Modulation of XCR1 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.



2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that the forkhead box D2, encoded by FOXD2, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast (4). FOXD2 was also differentially expressed in the tumor cells of patients with triple negative breast cancer (5). FOXD2 mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of FOXD2 in primary tumors was significantly correlated with patient recurrence-free survival. Modulation of FOXD2 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.



2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that secretagogin, encoded by SCGN, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast (4). Secretagogin was also differentially expressed in the tumor cells of patients with triple negative breast cancer (5). SCGN mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of SCGN in primary tumors was significantly correlated with patient recurrence-free survival. Modulation of SCGN expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.



2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that the ankyrin repeat, SAM and basic leucine zipper domain containing 1, encoded by ASZ1, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast (4). ASZ1 was also differentially expressed in the tumor cells of patients with triple negative breast cancer (5). ASZ1 mRNA was present at decreased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of ASZ1 in primary tumors was significantly correlated with patient post-progression survival. Modulation of ASZ1 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.



2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that the enhancer of rudimentary homolog, encoded by ERH, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast (4). ERH was also differentially expressed in the tumor cells of patients with triple negative breast cancer (5). ERH mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of ERH in primary tumors was significantly correlated with patient recurrence-free survival. Modulation of ERH expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.



2014 ◽  
Vol 74 (S 01) ◽  
Author(s):  
M Wallwiener ◽  
AD Hartkopf ◽  
S Riethdorf ◽  
J Nees ◽  
FA Taran ◽  
...  


2016 ◽  
Vol 76 (10) ◽  
Author(s):  
R Lampignano ◽  
M Neumann ◽  
B Behrens ◽  
D Köhler ◽  
D Niederacher ◽  
...  




2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that Rab11 family-interacting protein 4, encoded by RAB11FIP4, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. RAB11FIP4 mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of RAB11FIP4 in primary tumors was significantly correlated with patient recurrence-free survival and distant metastasis-free survival. Modulation of RAB11FIP4 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.



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