Induction of breast cancer stem cells by M1 macrophages through Lin-28B-let-7-HMGA2 axis

Guo, Liang; Cheng, Xiang; Chen, Hongyu; Chen, Changguo; Xie, Sheng; Zhao, Min; Liú, Dan; Deng, Que; Liu, Yanjun; Wang, Xiaomeng; Chen, Xintian; Wang, Jian-Gong; Yin, Zhaoyang; Qi, Siyong; Gao, Jiangping; Ma, Yuanfang; Guo, Ning; Shi, Ming

doi:10.1016/j.canlet.2019.03.032

Cited by 67 publications

(48 citation statements)

References 65 publications

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“…Similar to Flow cytometric analysis, YTE‐17 significantly restrained M2 marker (Arg‐1) and enhanced M1 marker (iNOS) expression, respectively (Figure 3B up). Extensive evidence suggests that the phosphorylation of some known signaling pathways, including ERK, JNK, and STAT3, is markedly enhanced by tumor supernatant stimulation in RAW264.7 cells 34-36 . To further explore the potential mechanism of YTE‐17, we used in vitro models to identify the pathway that could be regulated as YTE‐17 inhibits M2 macrophage polarization.…”

Section: Resultsmentioning

confidence: 99%

The active fraction of Garcinia yunnanensis suppresses the progression of colorectal carcinoma by interfering with tumorassociated macrophage‐associated M2 macrophage polarization in vivo and in vitro

Sui

Tan

et al. 2020

FASEB j.

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Colorectal cancer (CRC) is the third most common solid tumor worldwide and has shown resistance to several immunotherapies, particularly immune checkpoint blockade therapy, which is effective in many other types of cancer. Our previous studies indicated that the active fraction of Garcinia yunnanensis (YTE‐17), had potent anticancer activities by regulating multiple signaling pathways. However, knowledge regarding the mechanism and effect of YTE‐17 in the prevention of CRC is limited. This study tested the effects of YTE‐17 on colon cancer development in vivo by using two murine models: the carcigenic azoxymethane/dextran sulfate sodium (AOM/DSS)‐induced CRC model and a genetically induced model using ApcMin/+ mice. Here, the tumor load, tumor number, histology, and even some oncogenes were used to evaluate the effect of YTE‐17. The intragastric administration of YTE‐17 for 12 weeks significantly decreased CRC incidence, tumor number and size, immunity, and some tumor‐associated macrophage (TAM) markers, including CD206, Arg‐1, IL‐10, and TGF‐β. Importantly, the macrophages depletion by clodronate (CEL) also played a role in reducing the tumor burden and inhibiting tumor development, which were not affected by YTE‐17 in the ApcMin/+ mice. Moreover, the YTE‐17 treatment attenuated CRC cell growth in a co‐culture system in the presence of macrophages. Consistently, YTE‐17 effectively reduced the tumor burden and macrophage infiltration and enhanced immunity in the AOM/DSS and ApcMin/+ colon tumor models. Altogether, we demonstrate that macrophages in the microenvironment may contribute to the development and progression of CRC cells and propose YTE‐17 as a new potential drug option for the treatment of CRC.

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Section: Resultsmentioning

confidence: 99%

The active fraction of Garcinia yunnanensis suppresses the progression of colorectal carcinoma by interfering with tumorassociated macrophage‐associated M2 macrophage polarization in vivo and in vitro

Sui

Tan

et al. 2020

FASEB j.

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“…Li et al demonstrated that HMGA2 was present at high-levels and interacted with nucleosomes in human embryonic stem cells [ 15 ]. In addition, proinflammatory macrophages (M1) were found to be crucial in formation and maintenance of cancer stem cells (CSCs), where HMGA2 could induce M1-mediated CSC phenotype in breast cancer [ 16 ]. Interestingly, as another HMGA family member, HMGA1 was reported to play essential roles in ISC (intestinal stem cell) maintenance and function.…”

Section: Introductionmentioning

confidence: 99%

Emerging roles for HMGA2 in colorectal cancer

Wang

2021

Translational Oncology

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HMGA2 (High Mobility Group AT-hook 2) has been reported to promote colorectal cancer (CRC) development by regulating the transcription of target genes. It participates in nearly all aspects of cellular processes, including cell transformation, proliferation, apoptosis, senescence, metastasis, epithelial-to-mesenchymal transition (EMT), DNA repair and stem cell self-renewal. In the past decades, a group of downstream targets and binding partners have been identified in a wide range of cancers. Our findings of HMGA2 as a key factor in the MDM2/p53, IL11/STAT3 and Wnt/β-catenin signaling pathways prompt us to summarize current advances in the functional and molecular basis of HMGA2 in CRC. In this review, we address the roles of HMGA2 in the oncogenic networks of CRC based on recent advances. We review its aberrant expression, explore underlying mechanisms, discuss its pro-tumorigenic effects, and highlight promising small-molecule inhibitors based on targeting HMGA2 here. However, the understanding of HMGA2 in CRC progression is still elusive, thus we also discuss the future perspectives in this review. Collectively, this review provides novel insights into the oncogenic properties of HMGA2, which has potential implications in the diagnosis and treatment of CRC.

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“…This is corroborated epidemiologically by the association of obesity with higher cancer risk (40) and poor prognosis (4) of PM/ER - /PR - breast cancer patients. Our findings thus provide a cancer cell autonomous mechanism for the increased appreciation that obese environments lead to enhanced tumor formation capacity in breast cancer (7,11,41–43). Our findings further expand on the molecular mechanisms of PA-induced stemness, by demonstrating that that obesity-induced stemness is mediated through the epigenetic activation of a C/EBPB dependent transcriptional network.…”

Section: Discussionmentioning

confidence: 74%

C/EBPB-dependent Adaptation to Palmitic Acid Promotes Tumor Formation in Hormone Receptor Negative Breast Cancer

Liu

Rulina

Choi

et al. 2020

Preprint

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Epidemiological studies have established a positive association between obesity and the incidence of postmenopausal (PM) breast cancer. However, the molecular mechanisms underlying this correlation are not well defined. A central phenotypic characteristic of obese individuals is increased circulating and interstitial abundance of free fatty acids. Here we demonstrate that long-term exposure to palmitic acid (PA) drives cancer cell dedifferentiation towards a cancer stem-like phenotype and enhanced tumor formation capacity. We demonstrate that this process is governed epigenetically through increased chromatin occupancy of CCAAT/enhancer-binding protein beta (C/EBPB). C/EBPB regulates cancer stem-like properties by modulating the expression of key downstream regulators of the extracellular matrix (ECM) including SERPINB2 and LCN2. Collectively, our findings demonstrate that C/EBPB plays a critical role in the initiation of cancer cells in obesity.

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Induction of breast cancer stem cells by M1 macrophages through Lin-28B-let-7-HMGA2 axis

Cited by 67 publications

References 65 publications

The active fraction of Garcinia yunnanensis suppresses the progression of colorectal carcinoma by interfering with tumorassociated macrophage‐associated M2 macrophage polarization in vivo and in vitro

The active fraction of Garcinia yunnanensis suppresses the progression of colorectal carcinoma by interfering with tumorassociated macrophage‐associated M2 macrophage polarization in vivo and in vitro

Emerging roles for HMGA2 in colorectal cancer

C/EBPB-dependent Adaptation to Palmitic Acid Promotes Tumor Formation in Hormone Receptor Negative Breast Cancer

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