Aldolase B-Mediated Fructose Metabolism Drives Metabolic Reprogramming of Colon Cancer Liver Metastasis

Bu, Pengcheng; Chen, Kai-Yuan; Xiang, Kun; Johnson, Chloe; Crown, Scott B.; Rakhilin, Nikolai; Ai, Yiwei; Wang, Lihua; Rui, Xiaoting; Astapova, Inna; Han, Yan; Li, Jiahe; Barth, Bradley B.; Lu, Min; Gao, Ziyang; Mines, Robert; Zhang, Liwen; Herman, Mark A.; Hsu, David S.; Zhang, Guofang; Shen, Xiling

doi:10.1016/j.cmet.2018.04.003

Cited by 202 publications

(175 citation statements)

References 71 publications

(85 reference statements)

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“…Cancer metastasis accounts for the majority of cancer‐related deaths and remains a clinical challenge. During the development of CRC, cancer cells can progress through adenoma‐cancer‐cancer sequences, which ultimately leads to preferential transfer to the liver . However, liver metastasis is the leading cause of death in patients with CRC .…”

Section: Gata6 and Human Cancersmentioning

confidence: 99%

“…However, liver metastasis is the leading cause of death in patients with CRC . In particular, abnormally high expression of GATA6 is closely associated with poor prognosis and liver metastasis of CRC . The occurrence of CRC is related to genetic factors, diet, family history, smoking and drinking, and the disease‐causing gene has received increasing attention.…”

Section: Gata6 and Human Cancersmentioning

confidence: 99%

“…During the development of CRC, cancer cells can progress through adenoma-cancer-cancer sequences, which ultimately leads to preferential transfer to the liver. 88 However, liver metastasis is the leading cause of death in patients with CRC. 89 In particular, abnormally high expression of GATA6 is closely associated with poor prognosis and liver metastasis of CRC.…”

Section: Gata6 and Colorectal Cancermentioning

confidence: 99%

“…89 In particular, abnormally high expression of GATA6 is closely associated with poor prognosis and liver metastasis of CRC. 88,89 The occurrence of CRC is related to genetic factors, diet, family history, smoking and drinking, and the disease-causing gene has received increasing attention. In the future, the study of the GATA6 gene will focus more on the early diagnosis of CRC, because early detection of cancer will greatly contribute to the cure of CRC.…”

Section: Gata6 and Colorectal Cancermentioning

confidence: 99%

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Multiple roles and regulatory mechanisms of the transcription factor GATA6 in human cancers

Sun

Yan

2019

Clinical Genetics

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Cancer is a common type of non-communicable disease, and its morbidity and mortality are rapidly increasing. It is expected to become the largest obstacle to the promotion of global human health in the future. Some transcription factors that play important regulatory roles in embryogenesis and subsequent tissue maintenance can be selectively amplified during tumorigenesis. Due to its high expression in the embryonic endoderm and mesoderm, GATA6 plays a crucial role in the normal development of early human heart, lung, digestive system, adrenal glands, breasts, ovaries, retina, skin, and nervous system. Up to now, overexpression of the GATA6 gene has been shown to play an important role in several cancers, including lung cancer, digestive system tumors, breast cancer, and ovarian cancer. However, the human body is a complex organism, which causes the transcription factor GATA6 to have multiple roles in cancer. In this review, we summarize the multiple roles of transcription factor GATA6 in various cancers and its regulatory mechanisms. The aim is to better understand the relationship between GATA6 gene expression and cancer development and to provide new insights for exploring potential therapeutic targets.

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Section: Gata6 and Human Cancersmentioning

confidence: 99%

Section: Gata6 and Human Cancersmentioning

confidence: 99%

Section: Gata6 and Colorectal Cancermentioning

confidence: 99%

Section: Gata6 and Colorectal Cancermentioning

confidence: 99%

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Multiple roles and regulatory mechanisms of the transcription factor GATA6 in human cancers

Sun

Yan

2019

Clinical Genetics

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“…Colon cancer is a malignancy of multiple stages, and other than gene mutations such as KRAS, BRAF, TP53, and DNA mismatch pair genes, chronic inflammation is recognized as a major cause for the development of colon cancer (Chen et al, ; Hale et al, ; Imperial et al, ). Although surgical resection combined with adjuvant therapy is efficient at early stages of the disease, subsequent relapse and metastasis such as liver and lung metastasis often occur, which is an important reason for deaths of patients (Bu et al, ; J. Li et al, ). Therefore, it is significant to uncover the underlying mechanisms and provide proper therapies for metastatic colon cancer.…”

Section: Introductionmentioning

confidence: 99%

c‐Fos separation from Lamin A/C by GDF15 promotes colon cancer invasion and metastasis in inflammatory microenvironment

Ding

Hao

et al. 2019

Journal Cellular Physiology

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Inflammatory microenvironment is an important factor for promoting cancer invasion and metastasis, but the underlying molecular mechanisms remain unclear. Here, we mimicked an inflammatory microenvironment both in vitro and in vivo and investigated its effects on the invasion and metastasis of colon cancer. Moreover, colon cancer patient samples were also analyzed statistically. Conditioned medium from the differentiated macrophages induced invasion and migration of colon cancer cells in vitro, which could be reversed by the treatment of a neutralizing anti-growth differentiation factor 15 (GDF15) antibody, indicating GDF15 involvement in inflammation-induced invasiveness. Also, we observed similar effects of human recombinant GDF15 on colon cancer cells. Mechanistically, GDF15 activated c-Fos by separating it from Lamin A/C, increasing transcriptional activity of c-Fos and regulating EMT gene expressions. However, c-Fos knockdown using lentivirus shRNA plasmid inhibited GDF15-triggered invasion and migration in vitro. In vivo, inflammation caused by lipopolysaccharides obviously increased GDF15 secretion, and c-Fos knockdown reduced the lung metastasis of colon cancer cells in mice model. In addition, c-Fos expressions in patient samples were found to be associated with colon cancer metastasis and TNM stages. Taken together, GDF15 in inflammatory microenvironment induces colon cancer invasion and metastasis by regulating EMT genes by activating c-Fos, which might be a potential therapeutic target for metastatic colon cancer. K E Y W O R D S EMT, Erk1/2, Lamin A/C/c-Fos signaling axis, macrophages-derived cytokine Abbreviations: CM, conditioned medium; DAPI, diamidinophenylindole; EMSA, electrophoretic mobility shift assays; EMT, epithelial-mesenchymal transition; GDF15, growth differentiation factor 15; H&E, hematoxylin and eosin; IH C, immunohistochemistry; LPS, lipopolysaccharides; PMA, phorbol 12-myristate 13-acetate; RM, regular medium; TAMs, tumor-associated macrophages. *Youxiang Ding and Kun Hao contributed equally to this work. SUPPORTING INFORMATIONAdditional supporting information may be found online in the Supporting Information section.How to cite this article: Ding Y, Hao K, Li Z, et al. c-Fos separation from Lamin A/C by GDF15 promotes colon cancer invasion and metastasis in inflammatory microenvironment.

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Cancer Metabolism

Pavlova¹,

Rao²,

DeBerardinis³

et al. 2022

Holland‐Frei Cancer Medicine

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Overview Successful cell proliferation is dependent on a profound remodeling of cellular metabolism, required to support the biosynthetic needs of a growing cell. Constitutive signaling through aberrantly activated oncogenes activates pro‐growth metabolic circuits that can lock cancer cells into net macromolecular synthesis and resistance to cell death. Oncogenic signaling can induce cellular uptake of metabolic substrates, such as glucose and glutamine, as well as utilization of unconventional nutrient sources. In contrast to some nonproliferating tissues, which preferentially degrade metabolic substrates to carbon dioxide to maximize energy production, cancer cells prioritize the use of acquired metabolic substrates in anabolic processes, including fatty acid, cholesterol, nonessential amino acid, and nucleotide biosynthesis. The accumulation of these precursors supports the synthesis of the macromolecules necessary to sustain cell growth. Oncogene‐directed increases in levels of select metabolites can also influence cellular processes beyond metabolic circuits, resulting in changes to the cellular epigenetic state as well as long‐ranging effects on cells within the tumor microenvironment. As cancer progresses, the metabolic properties and liabilities of malignant cells evolve to support metastasis and therapy resistance. Recent studies suggest these alterations in tumor cell metabolism can be exploited to improve the diagnosis and treatment of a wide variety of cancers.

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Aldolase B-Mediated Fructose Metabolism Drives Metabolic Reprogramming of Colon Cancer Liver Metastasis

Cited by 202 publications

References 71 publications

Multiple roles and regulatory mechanisms of the transcription factor GATA6 in human cancers

Multiple roles and regulatory mechanisms of the transcription factor GATA6 in human cancers

c‐Fos separation from Lamin A/C by GDF15 promotes colon cancer invasion and metastasis in inflammatory microenvironment

Cancer Metabolism

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