scholarly journals Fatty acid β-oxidation promotes breast cancer stemness and metastasis via the miRNA-328-3p-CPT1A pathway

2021 ◽  
Author(s):  
Feng Zeng ◽  
Mingkang Yao ◽  
Yun Wang ◽  
Wei Zheng ◽  
Shengshan Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Target Gene ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Breast Cancer Patients ◽  
Potential Therapeutic Target ◽  
Downstream Target ◽  
Downstream Target Gene ◽  
Breast Cancer Growth

AbstractMicroRNAs (miRNA) have been shown to be associated with tumor diagnosis, prognosis, and therapeutic response. MiR-328-3p plays a significant role in breast cancer growth; however, its actual function and how it modulates specific biological functions is poorly understood. Here, miR-328-3p was significantly downregulated in breast cancer, especially in patients with metastasis. Mitochondrial carnitine palmitoyl transferase 1a (CPT1A) is a downstream target gene in the miR-328-3p-regulated pathway. Furthermore, the miR-328-3p/CPT1A/fatty acid β-oxidation/stemness axis was shown responsible for breast cancer metastasis. Collectively, this study revealed that miR-328-3p is a potential therapeutic target for the treatment of breast cancer patients with metastasis, and also a model for the miRNA-fatty acid β-oxidation-stemness axis, which may assist inunderstanding the cancer stem cell signaling functions of miRNA.

scholarly journals Histone deacetylase 11 inhibition promotes breast cancer metastasis from lymph nodes

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Patrick L. Leslie ◽  
Yvonne L. Chao ◽  
Yi-Hsuan Tsai ◽  
Subrata K. Ghosh ◽  
Alessandro Porrello ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Histone Deacetylase ◽  
Cancer Metastasis ◽  
Hdac Inhibitors ◽  
Distant Metastases ◽  
Breast Cancer Metastasis ◽  
Breast Cancer Patients ◽  
Metastasis Development ◽  
Breast Cancer Growth ◽  
Worse Prognosis

Abstract Lymph node (LN) metastases correspond with a worse prognosis in nearly all cancers, yet the occurrence of cancer spreading from LNs remains controversial. Additionally, the mechanisms explaining how cancers survive and exit LNs are largely unknown. Here, we show that breast cancer patients frequently have LN metastases that closely resemble distant metastases. In addition, using a microsurgical model, we show how LN metastasis development and dissemination is regulated by the expression of a chromatin modifier, histone deacetylase 11 (HDAC11). Genetic and pharmacologic blockade of HDAC11 decreases LN tumor growth, yet substantially increases migration and distant metastasis formation. Collectively, we reveal a mechanism explaining how HDAC11 plasticity promotes breast cancer growth as well as dissemination from LNs and suggest caution with the use of HDAC inhibitors.

A rare solitary breast cancer metastasis to the soft tissue of the ipsilateral arm detected by a physiotherapist: A case report

2021 ◽  
Vol 41 (2) ◽  
pp. 187-191
Author(s):  
Ramesh Omranipour ◽  
Sadaf Alipour ◽  
Bita Eslami
Keyword(s):  
Breast Cancer ◽  
Soft Tissue ◽  
Cancer Metastasis ◽  
Multidisciplinary Treatment ◽  
Breast Cancer Metastasis ◽  
Frequency Interval ◽  
Treatment Team ◽  
Breast Cancer Patients ◽  
Rare Presentation ◽  
Adequate Treatment

BACKGROUND: Late occurrence of solitary soft tissue upper extremity metastasis of breast cancer is very rare. We hereby present a case of metastasis to the biceps muscle of the ipsilateral arm, detected by a physiotherapist six years after mastectomy. The aim of this report is to highlight the rarity of this presentation, to emphasize the role of the physiotherapist as a member of the multidisciplinary treatment team and the possibility of curative treatment despite the poor prognosis. CASE DESCRIPTION: A 2 * 3 cm well-defined isolated metastasis of breast cancer was diagnosed in the left arm of a 31-year-old woman 6 years after successful treatment of her primary tumor. Tumor characteristics, diagnostic plan, and treatment options are discussed. CONCLUSION: Due to its scarcity, there is a lack of knowledge about the frequency, interval, characteristics, best diagnostic modality, adequate treatment, and prognosis of isolated breast cancer metastasis to the soft tissue, and these can be found out by proper reporting. As an important member of the multidisciplinary team in the care and treatment of breast cancer patients, physiotherapists should be aware of this type of rare presentation.

scholarly journals E2F1 Drives Breast Cancer Metastasis by Regulating the Target Gene FGF13 and Altering Cell Migration

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Daniel P. Hollern ◽  
Matthew R. Swiatnicki ◽  
Jonathan P. Rennhack ◽  
Sean A. Misek ◽  
Brooke C. Matson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Target Gene ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis

scholarly journals Mitochondrial Malic Enzyme 2 Promotes Breast Cancer Metastasis via Stabilizing HIF-1α Under Hypoxia

2021 ◽  
Author(s):  
Duo You ◽  
Danfeng Du ◽  
Xueke Zhao ◽  
Xinmin Li ◽  
Minfeng Ying ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
High Expression ◽  
Breast Cancer Patients ◽  
Cancer Model ◽  
Breast Cancer Model

Abstract Background: α-ketoglutarate (α-KG) is the substrate to hydoxylate collagen and hypoxia-inducible factor-1α (HIF-1α), which are important for cancer metastasis. Previous studies showed that upregulation of collagen prolyl 4-hydroxylase in breast cancer cells stabilizes HIF-1α via depleting α-KG in breast cancer cells. We propose that mitochondrial malate enzyme 2 (ME2) may also affect HIF-1α via modulating α-KG level in breast cancer cells. Methods: ME2 protein expression was evaluated by immunohistochemistry on 100 breast cancer patients and correlated with clinicopathological indicators. The effect of ME2 knockout on cancer metastasis was evaluated by an orthotopic breast cancer model. The effect of ME2 knockout or knockdown on the levels of α-KG and HIF-1α protein in breast cancer cell lines (4T1 and MDA-MB-231) was determined in vitro and in vivo.Results: The high expression of ME2 was observed in the human breast cancerous tissues compared to the matched precancerous tissues (P=0.000). The breast cancer patients with a high expression of ME2 had an inferior survival than the patients with low expression of ME2 (P=0.019). ME2 high expression in breast cancer tissues was also related with lymph node metastasis (P=0.016), pathological staging (P=0.033) and vascular cancer embolus (P=0.014). In a 4T1 orthotopic breast cancer model, ME2 knockout significantly inhibited lung metastasis. In the tumors formed by ME2 knockout 4T1 cells, α-KG level significantly increased, collagen hydroxylation level did not change significantly, but HIF-1α protein level significantly decreased, in comparison to control. In cell culture, ME2 knockout or knockdown cells demonstrated a significantly higher α-KG level but significantly lower HIF-1α protein level than control cells under hypoxia. Exogenous malate and α-KG exerted similar effect on HIF-1α in breast cancer cells to ME2 knockout or knockdown. Treatment with malate significantly decreased 4T1 breast cancer lung metastasis. ME2 expression was associated with HIF-1α level in human breast cancer samples (P=0.027).Conclusion: We provide evidence that upregulation of ME2 is associated with a poor prognosis of breast cancer patients and propose a mechanistic understanding of a link between ME2 and breast cancer metastasis.

scholarly journals Fatty acid synthase promotes breast cancer metastasis by mediating changes in fatty acid metabolism

2020 ◽  
Vol 21 (1) ◽  
pp. 1-1
Author(s):  
Shuo Xu ◽  
Tingting Chen ◽  
Lihua Dong ◽  
Tao Li ◽  
Hui Xue ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Fatty Acid Synthase ◽  
Cancer Metastasis ◽  
Acid Metabolism ◽  
Breast Cancer Metastasis

scholarly journals Clinical Impact of Sphingosine-1-Phosphate in Breast Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Junko Tsuchida ◽  
Masayuki Nagahashi ◽  
Kazuaki Takabe ◽  
Toshifumi Wakai
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Metastasis ◽  
Clinical Importance ◽  
Breast Cancer Metastasis ◽  
Lipid Mediator ◽  
Breast Cancer Patients ◽  
Cellular Functions ◽  
Sphingosine 1 Phosphate ◽  
Underlying Mechanisms

Breast cancer metastasizes to lymph nodes or other organs, which determine the prognosis of patients. It is difficult to cure the breast cancer patients with distant metastasis due to resistance to drug therapies. Elucidating the underlying mechanisms of breast cancer metastasis and drug resistance is expected to provide new therapeutic targets. Sphingosine-1-phosphate (S1P) is a pleiotropic, bioactive lipid mediator that regulates many cellular functions, including proliferation, migration, survival, angiogenesis/lymphangiogenesis, and immune responses. S1P is formed in cells by sphingosine kinases and released from them, which acts in an autocrine, paracrine, and/or endocrine manner. S1P in extracellular space, such as interstitial fluid, interacts with components in the tumor microenvironment, which may be important for metastasis. Importantly, recent translational research has demonstrated an association between S1P levels in breast cancer patients and clinical outcomes, highlighting the clinical importance of S1P in breast cancer. We suggest that S1P is one of the key molecules to overcome the resistance to the drug therapies, such as hormonal therapy, anti-HER2 therapy, or chemotherapy, all of which are crucial aspects of a breast cancer treatment.

BRMS1L inhibits bone metastasis of breast cancer cells through epigenetic silence of CXCR4.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13002-e13002
Author(s):  
Yinghuan Cen ◽  
Chang Gong ◽  
Jun Li ◽  
Gehao Liang ◽  
Zihao Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Qrt Pcr ◽  
Metastatic Sites

e13002 Background: We previously demonstrated that BRMS1L (breast cancer metastasis suppressor 1 like) suppresses breast cancer metastasis through HDAC1 recruitment and histone H3K9 deacetylation at the promoter of FZD10, a receptor for Wnt signaling. It is still unclear whether BRMS1L regulates organ-specific metastases, such as bone metastasis, the most prevalent metastatic site of breast cancer. Methods: Examination of the expression of BRMS1L in primary tumors, bone metastatic and other metastatic tissues from breast cancer patients was implemented using qRT-PCR and immunohistochemistry staining. To investigate the mechanism by which BRMS1L drives breast cancer bone metastasis, we tested the mRNA expression by qRT-PCR of a set of potential bone related genes (BRGs) based on PubMed database in MDA-MB-231 cells over expressing BRMS1L and MCF-7 cells knocking-down BRMS1L, and detected the expression of CXCR4 in these established cells by western blot. Transwell assays were performed to assess the migration abilities of breast cancer cells towards osteoblasts. ChIP (Chromatin Immuno-Precipitation) were employed to test the interaction between BRMS1L and CXCR4. Results: At both mRNA and protein levels, the expression of BRMS1L was significantly lower in bone metastatic sites than that in primary cancer tissues and other metastatic sites of breast cancer patients. CXCR4 was screened out in a set of BRGs and negatively correlated with the expression of BRMS1L in breast cancer cell lines. BRMS1L inhibited the migration of breast cancer cells towards osteoblasts through CXCL12/CXCR4 axis. In the presence of TSA treatment, breast cancer cell lines showed an increased expression of CXCR4 in a TSA concentration-dependent manner. In addition, ChIP assays verified that BRMS1L directly bound to the promoter region of CXCR4 and inhibited its transcription through promoter histone deacetylation. Conclusions: BRMS1L mediates the migration abilities of breast cancer cells to bone microenvironment via targeting CXCR4 and contributes to bone metastasis of breast cancer cells. Thus, BRMS1L may be a potential biomarker for predicting bone metastasis in breast cancer.

Exploring the determinants of delayed diagnosis of breast cancer in the female population of Punjab (Pakistan)

2021 ◽  
Author(s):  
Samina Farooqi ◽  
Samina Kausar ◽  
Kalsoom Bibi ◽  
Zunaira Aziz ◽  
Tahira Rehmat
Keyword(s):  
Breast Cancer ◽  
Health Care ◽  
Cancer Metastasis ◽  
Delayed Diagnosis ◽  
Care Facility ◽  
Breast Cancer Metastasis ◽  
Diagnosis Delay ◽  
Breast Cancer Patients ◽  
Related Factors ◽  
Female Population

ABSTRACT Objective: To explore the factors contributing to late diagnosis of breast cancer in female population of Punjab, Pakistan. Methodology: Descriptive qualitative study with phenomenological approach was used. The study was carried out in University of Health Sciences, Lahore in collaboration with breast cancer clinics/departments of the Jinnah Hospital, Lahore, Sir Ganga Ram Hospital Lahore and Mayo Hospital Lahore. 15 Females diagnosed more than 4 months after appearance of symptoms of breast cancer were recruited using purposive sampling until saturation of data. Data collected through in depth semi structured face to face interviews was tape-recorded, transcribed and then analysed using thematic analysis framework method. Results: Personal/psychological factors, Sociocultural and Health care system related factors were identified as main themes emerged from data. Lack of knowledge, religious believes, use of Alternative medicine, socioeconomic status cultural myths and poorly facilitated health care facility were the most influential determinants of delay among breast cancer patients. Conclusion: Diagnosis delay is very significant health problem in women with breast cancer linked with multiple determinants. However, educating women for recognition of symptoms and reinforcement to pursue for earlier medical consultation will be helpful in reducing breast cancer diagnosis delay in the country. Key terms: Breast Cancer, Metastasis, Delayed Diagnosis, Prognosis, Advance Stage.

Serum ANGPTL2 Levels Reflect Clinical Features of Breast Cancer Patients: Implications for the Pathogenesis of Breast Cancer Metastasis

2014 ◽  
Vol 29 (3) ◽  
pp. 239-245 ◽  
Author(s):  
Motoyoshi Endo ◽  
Yutaka Yamamoto ◽  
Masahiro Nakano ◽  
Tetsuro Masuda ◽  
Haruki Odagiri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Features ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Ductal Carcinoma ◽  
Breast Cancer Metastasis ◽  
Breast Cancer Patients

Introduction Breast cancer is a leading cause of cancer-related death in women worldwide, and its metastasis is a major cause of disease mortality. Therefore, identification of the mechanisms underlying breast cancer metastasis is crucial for the development of therapeutic and diagnostic strategies. Our recent study of immunodeficient female mice transplanted with MDA-MB231 breast cancer cells demonstrated that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) accelerates metastasis through both increasing tumor cell migration in an autocrine/paracrine manner, and enhancing tumor angiogenesis. To determine whether ANGPTL2 contributes to its clinical pathogenesis, we asked whether serum ANGPTL2 levels reflect the clinical features of breast cancer progression. Methods We monitored the levels of secreted ANGPTL2 in supernatants of cultured proliferating MDA-MB231 cells. We also determined whether the circulating ANGPTL2 levels were positively correlated with cancer progression in an in vivo breast cancer xenograft model using MDA-MB231 cells. Finally, we investigated whether serum ANGPTL2 levels were associated with clinical features in breast cancer patients. Results Both in vitro and in vivo experiments showed that the levels of ANGPTL2 secreted from breast cancer cells increased with cell proliferation and cancer progression. Serum ANGPTL2 levels in patients with metastatic breast cancer were significantly higher than those in healthy subjects or in patients with ductal carcinoma in situ or non-metastatic invasive ductal carcinoma. Serum ANGPTL2 levels in patients negative for estrogen receptors and progesterone receptors, particularly triple-negative cases, reflected histological grades. Conclusions These findings suggest that serum ANGPTL2 levels in breast cancer patients could represent a potential marker of breast cancer metastasis.

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