Sodium/glucose cotransporter 1-dependent metabolic alterations induce tamoxifen resistance in breast cancer by promoting macrophage M2 polarization

Niu, Xingjian; Ma, Jianying; Li, Jingtong; Gu, Yucui; Yin, Lei; Wang, Yiran; Zhou, Xiaoping; Wang, Jinlu; Ji, Hongfei; Zhang, Qingyuan

doi:10.1038/s41419-021-03781-x

Cited by 41 publications

(29 citation statements)

References 30 publications

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“…For instance, Anders Etzerodt et al reported that CD163+ TAMs infiltration occurs in melanomas and is associated with the resistance of PD-1/PD-L1 therapy [ 68 ]. Studies indicated that nutrient deprivation in the TME impairs the functions of T cells or NK cells [ 69 ], and enforces macrophage polarization into TAMs through reprogramming their metabolic patterns [ 70 ]. Recent studies have shown that TAMs express elevated levels of the scavenger receptor CD36, accumulate lipid droplets, and utilize fatty acid oxidation (FAO) for energy generation to support tumor growth [ 71 ].…”

Section: Heterogeneous Tam Polarizationmentioning

confidence: 99%

The Impact of the Tumor Microenvironment on Macrophage Polarization in Cancer Metastatic Progression

Wang

Yung

Ngan

et al. 2021

IJMS

151

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Rather than primary solid tumors, metastasis is one of the hallmarks of most cancer deaths. Metastasis is a multistage event in which cancer cells escape from the primary tumor survive in the circulation and disseminate to distant sites. According to Stephen Paget's “Seed and Soil” hypothesis, metastatic capacity is determined not only by the internal oncogenic driving force but also by the external environment of tumor cells. Throughout the body, macrophages are required for maintaining tissue homeostasis, even in the tumor milieu. To fulfill these multiple functions, macrophages are polarized from the inflammation status (M1-like) to anti-inflammation status (M2-like) to maintain the balance between inflammation and regeneration. However, tumor cell-enforced tumor-associated macrophages (TAMs) (a high M2/M1 ratio status) are associated with poor prognosis for most solid tumors, such as ovarian cancer. In fact, clinical evidence has verified that TAMs, representing up to 50% of the tumor mass, exert both protumor and immunosuppressive effects in promoting tumor metastasis through secretion of interleukin 10 (IL10), transforming growth factor β (TGFβ), and VEGF, expression of PD-1 and consumption of arginine to inhibit T cell anti-tumor function. However, the underlying molecular mechanisms by which the tumor microenvironment favors reprogramming of macrophages to TAMs to establish a premetastatic niche remain controversial. In this review, we examine the latest investigations of TAMs during tumor development, the microenvironmental factors involved in macrophage polarization, and the mechanisms of TAM-mediated tumor metastasis. We hope to dissect the critical roles of TAMs in tumor metastasis, and the potential applications of TAM-targeted therapeutic strategies in cancer treatment are discussed.

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Section: Heterogeneous Tam Polarizationmentioning

confidence: 99%

The Impact of the Tumor Microenvironment on Macrophage Polarization in Cancer Metastatic Progression

Wang

Yung

Ngan

et al. 2021

IJMS

151

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“…Several components of TME, including hypoxia ( 41 ), cancer-associated fibroblasts ( 42 ), ECM ( 11 ), immune cells, and inflammatory cytokines such as IL-1β, transforming growth factor-β (TGF-β), and TNF-α ( 10 , 43 ) have been shown to be associated with endocrine resistance. Our team has also revealed some of the endocrine resistance mechanisms involving the immune microenvironment in previous studies such as that high SGLT1 expression mediates enhanced glucose uptake and lactic acid secretion, promoting M2-like tumor-associated macrophage (TAM) polarization and feedback activation of EGFR/PI3K/Akt/SGLT1 signaling in tumor cells to enhance tamoxifen resistance ( 44 ). Another article also proposed that TAMs increased the expression of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2), which promoted tamoxifen resistance ( 45 ).…”

Section: Discussionmentioning

confidence: 90%

Identification and validation of endocrine resistance-related and immune-related long non-coding RNA (lncRNA) signatures for predicting endocrinotherapy response and prognosis in breast cancer

Yang¹,

Sun²,

Ji³

et al. 2022

Ann Transl Med

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Background: Endocrine resistance remains a major challenge in breast cancer (BRCA). Increasing evidence has revealed that long non-coding RNA (lncRNA) are closely implicated in tumorigenesis, drug resistance, and the immune-related pathways of cancer. However, the immune-related lncRNA remains to be thoroughly investigated in predicting the endocrine therapeutic response and prognosis of BRCA.Methods: Based on the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, and calculating the correlation of lncRNAs with immune-related genes obtained from ImmPort and InnateDB databases, we finally obtained endocrine resistance-related and immune-related long noncoding RNAs (ERIR-lncRNAs). Univariate Cox and least absolute shrinkage and selection operator (LASSO) Cox regression were performed to screen prognosis-associated ERIR-lncRNAs and establish signatures, using 2 separate datasets from GEO for external validation. Principal component analysis (PCA), Kaplan-Meier analysis, receiver operating characteristic (ROC) curves, and multivariate Cox regression were performed to demonstrate the robustness and predictability of the signature. We investigated tumor immune infiltration and tumor mutation burden (TMB) between high-and low-risk groups, and the role of key lncRNAs in endocrine resistant breast cancer was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR), Cell Counting Kit 8 (CCK 8) and transwell assays.Results: A total of 781 endocrine resistance related lncRNAs were identified, of which 12 lncRNAs were associated with immunity. Then, three ERIR-lncRNAs with prognostic relevance were screened to successfully construct the risk signature. Compared to sensitive patients, the endocrine resistant patients had higher risk scores in both the training and validation sets (P<0.05). The high-risk group had significantly shorter survival times (P<0.001) with area under the curve (AUC) values of 0.710, 0.649, and 0.672 at 1, 3, and 5 years. Univariate and multivariate Cox regression indicated that our signature was an independent prognostic factor (P<0.001). Through immune infiltration analysis, it was revealed that the high-risk scores were associated with T follicular helper (Tfh) differentiation and exhibited a pro-tumor phenomenon with ^ ORCID: 0000-0003-0649-2432.

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“…The transporter increases glycolytic flux and lactate production via aerobic glycolysis which induces a tumor-associated macrophage. The macrophage then promotes cell growth via EGFR/PI3K/Akt signaling, releasing immunosuppressive factors [ 44 ]. In line with the previous study, there is other evidence suggesting that high expression of SGLT1 correlates to a high growth rate of TNBC [ 45 ].…”

Section: Mrs Targeting Glucose Metabolismmentioning

confidence: 99%

Potential Therapies Targeting the Metabolic Reprogramming of Diabetes-Associated Breast Cancer

Shum

Vadgama

et al. 2023

JPM

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In recent years, diabetes-associated breast cancer has become a significant clinical challenge. Diabetes is not only a risk factor for breast cancer but also worsens its prognosis. Patients with diabetes usually show hyperglycemia and hyperinsulinemia, which are accompanied by different glucose, protein, and lipid metabolism disorders. Metabolic abnormalities observed in diabetes can induce the occurrence and development of breast cancer. The changes in substrate availability and hormone environment not only create a favorable metabolic environment for tumorigenesis but also induce metabolic reprogramming events required for breast cancer cell transformation. Metabolic reprogramming is the basis for the development, swift proliferation, and survival of cancer cells. Metabolism must also be reprogrammed to support the energy requirements of the biosynthetic processes in cancer cells. In addition, metabolic reprogramming is essential to enable cancer cells to overcome apoptosis signals and promote invasion and metastasis. This review aims to describe the major metabolic changes in diabetes and outline how cancer cells can use cellular metabolic changes to drive abnormal growth and proliferation. We will specifically examine the mechanism of metabolic reprogramming by which diabetes may promote the development of breast cancer, focusing on the role of glucose metabolism, amino acid metabolism, and lipid metabolism in this process and potential therapeutic targets. Although diabetes-associated breast cancer has always been a common health problem, research focused on finding treatments suitable for the specific needs of patients with concurrent conditions is still limited. Most studies are still currently in the pre-clinical stage and mainly focus on reprogramming the glucose metabolism. More research targeting the amino acid and lipid metabolism is needed.

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Sodium/glucose cotransporter 1-dependent metabolic alterations induce tamoxifen resistance in breast cancer by promoting macrophage M2 polarization

Cited by 41 publications

References 30 publications

The Impact of the Tumor Microenvironment on Macrophage Polarization in Cancer Metastatic Progression

The Impact of the Tumor Microenvironment on Macrophage Polarization in Cancer Metastatic Progression

Identification and validation of endocrine resistance-related and immune-related long non-coding RNA (lncRNA) signatures for predicting endocrinotherapy response and prognosis in breast cancer

Potential Therapies Targeting the Metabolic Reprogramming of Diabetes-Associated Breast Cancer

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