Fatty acid oxidation: driver of lymph node metastasis

AbstractFatty acid oxidation (FAO) is the emerging hallmark of cancer metabolism because certain tumor cells preferentially utilize fatty acids for energy. Lymph node metastasis, the most common way of tumor metastasis, is much indispensable for grasping tumor progression, formulating therapy measure and evaluating tumor prognosis. There is a plethora of studies showing different ways how tumor cells metastasize to the lymph nodes, but the role of FAO in lymph node metastasis remains largely unknown. Here, we summarize recent findings and update the current understanding that FAO may enable lymph node metastasis formation. Afterward, it will open innovative possibilities to present a distinct therapy of targeting FAO, the metabolic rewiring of cancer to terminal cancer patients.

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Role of metabolic reprogramming toward fatty acid oxidation on tumor lymph node metastasis.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e14501 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e14501-e14501

Author(s):

Choong-kun Lee ◽

Seung-hwan Jeong ◽

Cholsoon Jang ◽

Hosung Bae ◽

Yoo Hyung Kim ◽

...

Keyword(s):

Lymph Node ◽

Fatty Acid ◽

Tumor Cells ◽

Fatty Acid Oxidation ◽

Strong Predictor ◽

Metabolic Reprogramming ◽

Acid Oxidation ◽

Metastatic Tumors ◽

Genetic Ablation

e14501 Background: Metastasis of tumors to lymph node (LN) is a strong predictor of cancer patient mortality and determinant of disease progression and treatment options. Despite the clinical significance of tumor LN metastasis, the mechanisms underlying this process remain largely unexplored. Methods: We used comparative transcriptomics and metabolomics analyses of the primary tumor and LN micro- and macro-metastatic tumors from B16F10 murine melanoma model. B16F10 melanoma footpad implantation model and MMTV-PyMT spontaneous breast cancer genetic mouse models were analyzed in vivo. We also investigated the LN-metastatic tumors from sentinel LNs in 21 patients with melanoma. Results: We found that tumor cells undergo dramatic metabolic reprogramming towards fatty acid oxidation (FAO) for successful LN metastasis. Mechanistically, transcription co-activator YAP is selectively activated in LN metastatic tumors, leading to stimulation of FAO gene programs. Pharmacological inhibition of FAO or genetic ablation of YAP in tumors markedly suppressed LN metastasis. Unexpectedly, metastatic tumors highly stimulated the bile acid synthesis pathway upon arrival at the LN, and these bile acids activated YAP of tumor cells via nuclear vitamin D receptor. Lastly, YAP activation in the metastatic LNs of melanoma patients was reversely correlated with distant metastasis–free survival. Conclusions: This study propose that inhibition of FAO or YAP signaling to prevent the metabolic reprogramming of metastatic tumors offers a potential therapeutic strategy for mitigating tumor LN metastasis.

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Interrelations between hepatic fatty acid oxidation and gluconeogenesis: a possible regulatory role of carnitine palmityltransferase.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.58.2.790 ◽

1967 ◽

Vol 58 (2) ◽

pp. 790-797 ◽

Cited By ~ 30

Author(s):

G. Delisle ◽

I. B. Fritz

Keyword(s):

Fatty Acid ◽

Fatty Acid Oxidation ◽

Regulatory Role ◽

Acid Oxidation ◽

Hepatic Fatty Acid ◽

Hepatic Fatty Acid Oxidation

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Sentinel Node Biopsy: Interpretation and Management of Patients With Immunohistochemistry-Positive Sentinel Nodes and Those With Micrometastases

Journal of Clinical Oncology ◽

10.1200/jco.2007.14.4667 ◽

2008 ◽

Vol 26 (5) ◽

pp. 698-702 ◽

Cited By ~ 73

Author(s):

Emiel J.T. Rutgers

Keyword(s):

Lymph Node ◽

Lymph Node Metastasis ◽

Sentinel Node ◽

Tumor Cells ◽

Clinical Decision Making ◽

Prognostic Significance ◽

Axillary Lymph ◽

Isolated Tumor Cells ◽

Sentinel Nodes ◽

Node Metastasis

The sentinel node procedure is an adequate tool to identify lymph node metastasis in breast cancer. Sentinel nodes are generally examined with greater attention mainly to exclude, as reliably as possible, lymph node metastasis. To achieve this, many protocols are used, resulting in different rates of micrometastasis or isolated tumor cells encountered. Since the prognostic significance of isolated tumor cells or micrometastasis in the sentinel nodes, and the risk of further axillary lymph node involvement in patients with isolated tumor cells, is uncertain and at most limited, these findings may pose difficulties for clinicians in clinical decision making. Protocols that identify lymph node metastasis, from which the clinical relevance is known, are warranted. Unnecessary lymph node dissections should be avoided.

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Evaluation of the role of soluble B7-H3 in association with membrane B7-H3 expression in gastric adenocarcinoma

Cancer Biomarkers ◽

10.3233/cbm-210178 ◽

2021 ◽

pp. 1-7

Author(s):

Lili Huang ◽

Yan Zhou ◽

Qiuwei Sun ◽

Lei Cao ◽

Xueguang Zhang

Keyword(s):

Lymph Node ◽

Lymph Node Metastasis ◽

Tumor Cells ◽

Gastric Adenocarcinoma ◽

Tnm Stage ◽

Healthy Controls ◽

Infiltration Depth ◽

Tissue Samples ◽

Node Metastasis ◽

Pathological Characteristics

BACKGROUND and OBJECTIVE: Gastric adenocarcinoma (GAC) is one of the most common malignancies. Increasing data have indicated a correlation between soluble B7-H3 (sB7-H3) levels and tumor malignancies. In this study, we aim to investigate the level of soluble B7-H3 in serum of GAC patients. Further, we analyze the correlation between sB7-H3 level and tissue B7-H3 expression and explore the clinical evaluation value of sB7-H3 associated with pathological characteristics and prognosis of GAC patients. METHODS: One hundred and twenty-eight serum and tissue samples of GAC 20 serum and tissue samples of gastritis patients and 77 serum, 5 tissue samples of healthy controls were collected. The serum levels of sB7-H3 were detected by Enzyme-linked immunosorbent assay (ELISA), while the expression of membrane B7-H3 (mB7-H3) and Ki67 were evaluated by immunohistochemistry. The correlation between sB7-H3 and mB7-H3, sB7-H3 and Ki67, sB7-H3 or mB7-H3 and clinical features were analyzed by Pearson’s Chi-square test. RESULTS: Both serum level of sB7-H3 and tissue B7-H3 of GAC patients were significantly higher than those of gastritis patients and healthy controls. sB7-H3 level was correlated with total B7-H3 expression in tissues (r= 0.2801, P= 0.0014). Notably, the concentration of sB7-H3 was correlated with its expression of membrane form in tumor cells (r= 0.3251, P= 0.002) while not in stromal cells (r= 0.07676, P= 0.3891). Moreover, the levels of sB7-H3 in patients with TNM stage III/IV or with Infiltration depth T3/T4 or with lymph node metastasis were significantly higher than those of patients with TNM stage I/II (P= 0.0020) or with Infiltration depth T1/T2 (P= 0.0169) or with no lymph node metastasis (P= 0.0086). Tumor B7-H3 score, but not stromal B7-H3 score, in patients with TNM stage III/IV or with lymph node metastasis was significantly higher than those with TNM stage I/II (P= 0.0150) or with no lymph node metastasis (P= 0.182). CONCLUSIONS: Soluble B7-H3 level may reflect the tissue B7-H3 expression on tumor cells of GAC tissues. Elevated level of sB7-H3 in serum suggests poor clinical pathological characteristics of GAC patients.

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Abstract PS1-54: Risk factors for lymph node metastasis and the role of SLNB in microinvasive breast cancer

10.1158/1538-7445.sabcs20-ps1-54 ◽

2021 ◽

Author(s):

Pill Sun Paik ◽

Min Kyung Cho ◽

Juneyoung Ahn ◽

Chang Ik Yoon ◽

Tae-Kyung Yoo ◽

...

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Node Metastasis ◽

Microinvasive Breast Cancer

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The role of microvessel density, lymph node metastasis, and tumor size as prognostic factors of distant metastasis in colorectal cancer

Oncology Letters ◽

10.3892/ol.2017.5959 ◽

2017 ◽

Vol 13 (6) ◽

pp. 4327-4333 ◽

Cited By ~ 8

Author(s):

Tomonari Cho ◽

Eisuke Shiozawa ◽

Fumihiko Urushibara ◽

Nana Arai ◽

Toshitaka Funaki ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Factors ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Distant Metastasis ◽

Microvessel Density ◽

Tumor Size ◽

Node Metastasis

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FGFR3 promotes the growth and malignancy of melanoma by influencing EMT and the phosphorylation of ERK, AKT, and EGFR

BMC Cancer ◽

10.1186/s12885-019-6161-8 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 6

Author(s):

Lei Li ◽

Shuai Zhang ◽

Hao Li ◽

Haiyan Chou

Keyword(s):

Cell Proliferation ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Colony Formation ◽

Caspase 3 ◽

Growth Factor Receptor ◽

Invasion And Migration ◽

Node Metastasis ◽

And Migration

Abstract Background Overexpression of fibroblast growth factor receptor 3 (FGFR3) has been linked to tumor progression in many types of cancer. The role of FGFR3 in melanoma remains unclear. In this study, we aimed to uncover the role of FGFR3 in the growth and metastasis of melanoma. Methods FGFR3 knockdown and overexpression strategies were employed to investigate the effects of FGFR3 on colony formation, cell apoptosis, proliferation, migration, and in vitro invasion, along with the growth and metastasis of melanoma in a xenografts mouse model. The protein expression levels of extracellular signal-regulated kinase (ERK), protein kinase B (AKT), epidermal growth factor receptor (EGFR), and epithelial-mesenchymal transition (EMT) markers were determined by Western blot analysis. Results The mRNA expression of FGFR3 was higher in melanoma tissues than normal healthy tissues. FGFR3 expression in cutaneous malignant melanoma (CMM) tissues was positively correlated with the Breslow thickness and lymph node metastasis. In A357 cells, knockdown of the FGFR3 gene decreased the colony formation ability, cell proliferation, invasion, and migration, but increased the caspase 3 activity and the apoptosis rate; overexpression of FGFR3 increased the colony formation ability, cell proliferation, invasion, and migration, but decreased the caspase 3 activity and apoptosis rates. FGFR3 knockdown also upregulated E-cadherin, downregulated N-cadherin and vimentin, and decreased the phosphorylation levels of ERK, AKT, and EGFR. In the MCC xenografts mice, knockdown of FGFR3 decreased tumor growth and metastasis. Conclusions FGFR3, which is highly expressed in CMM tissues, is correlated with increased Breslow thickness and lymph node metastasis. FGFR3 promotes melanoma growth, metastasis, and EMT behaviors, likely by affecting the phosphorylation levels of ERK, AKT, and EGFR.

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