Review
Gastroenterology & Hepatology
Flora Yang, Leena Hilakivi-Clarke, Aurpita Shaha, Yuanguo Wang, Xianghu Wang, Yibin Deng, Jinping Lai, Ningling Kang
Summary: Cancer cells undergo metabolic reprogramming to adapt to hypoxic and hypo-nutrient conditions, leading to enhanced catabolism and anabolism. Liver cancers, including HCC and CCA, exhibit high heterogeneity in terms of metabolic alterations, with changes in glycolytic pathways and fatty acid metabolism. Understanding the metabolic features of liver cancer, including NAFLD, is crucial for identifying therapeutic targets and developing personalized treatments.
Review
Oncology
Chaofan Fan, Shing Kam, Pierluigi Ramadori
Summary: Liver cancer is a prevalent cancer type globally with limited treatment options. Metabolic and epigenetic abnormalities play crucial roles in the development of liver cancer, influencing the resilience and adaptability of tumor cells.
Review
Cell Biology
Macus Hao-Ran Bao, Carmen Chak-Lui Wong
Summary: Hypoxia, a hallmark of solid cancers like hepatocellular carcinoma, contributes to drug resistance through molecular mechanisms. This review focuses on HIF-mediated metabolic reprogramming in drug resistance in HCC and suggests combination therapies targeting hypoxia-induced metabolic enzymes to overcome resistance. Efforts to identify novel mechanisms to combat refractory hypoxic HCC are crucial for developing more effective treatment regimens.
Article
Cell Biology
Chong Zhang, Xiang-Yu Wang, Peng Zhang, Tao-Chen He, Jia-Hao Han, Rui Zhang, Jing Lin, Jie Fan, Lu Lu, Wen-Wei Zhu, Hu-Liang Jia, Ju-Bo Zhang, Jin-Hong Chen
Summary: This study identified HSPC111 as a key gene in promoting pre-metastatic niche formation and colorectal cancer liver metastasis (CRLM). HSPC111 altered the lipid metabolism of cancer-associated fibroblasts (CAFs), leading to the formation of a favorable microenvironment for cancer metastasis. This study suggests that targeting HSPC111 may be a potential therapeutic strategy for preventing CRLM.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Meilin Ma, Changhui Zhang, Rong Cao, Dongmei Tang, Xiongbo Sang, Sailan Zou, Xiuxuan Wang, Haixia Xu, Geng Liu, Lunzhi Dai, Yan Tian, Xiang Gao, Xianghui Fu
Summary: This study reveals the importance of UBE2O in the development of hepatocellular carcinoma (HCC). UBE2O is found to be highly expressed in HCC tumors and is associated with poor survival prognosis. It regulates lipid metabolic reprogramming by modulating the ubiquitination and degradation of HADHA, a mitochondrial enzyme. Furthermore, UBE2O deletion in mice inhibits hepatocarcinogenesis and reduces hepatic lipid accumulation.
Review
Cell Biology
M. Eugenia Delgado, Beatriz I. Cardenas, Nuria Farran, Mercedes Fernandez
Summary: This article summarizes the main components and mechanisms involved in the progression of liver fibrosis, with a special focus on the metabolic regulation of key effectors such as hepatic stellate cells (HSCs). It also discusses the role of RNA-binding proteins (RBPs) in the post-transcriptional regulation that affects the progression of fibrosis and chronic liver diseases (CLD).
Review
Oncology
Chunyu Zhao, Shanshuo Liu, Feng Gao, Yawen Zou, Zhigang Ren, Zujiang Yu
Summary: Primary liver cancer, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), is a significant cause of cancer-related mortality. Chemotherapy resistance in liver cancer has been linked to tumour microenvironment (TME) reprogramming. TME reprogramming can provide insights into cancer progression and regeneration, offering potential for novel treatment strategies.
FRONTIERS IN ONCOLOGY
(2022)
Review
Medicine, Research & Experimental
Zhenzhen Li, Chanjun Sun, Zhihai Qin
Summary: Cancer cells adapt their metabolism to proliferate and survive in harsh environments, with a close relationship between tumor microenvironment and cancer-associated fibroblasts (CAFs) playing key roles in tumor growth and metastasis. CAFs act as major regulators in shaping tumor metabolism, especially through dysregulation of metabolic pathways, influencing cancer cell behavior and response to therapy. The interaction and crosstalk between cancer cells and CAFs contribute to metabolic reprogramming that impacts cancer cell growth and progression.
Article
Oncology
Yeongmin Kim, So-Yeon Shin, Jihun Jeung, Yumin Kim, Yun-Won Kang, Sunjae Lee, Chang-Myung Oh
Summary: “Our analysis of publicly accessible cancer genome atlas datasets reveals the close association of cell cycle regulation, dysregulated lipid metabolism, and mitochondrial function with gastrointestinal malignancies COAD and LIHC. We identify mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) as a crucial regulator of cancer cell metabolism. These findings provide insights into the mechanisms underlying the development and progression of COAD and LIHC, and offer potential therapeutic targets for these malignancies.”
FRONTIERS IN ONCOLOGY
(2023)
Article
Gastroenterology & Hepatology
Min Chen, Yanke Lin, Yongkang Dang, Yifei Xiao, Fugui Zhang, Guanghui Sun, Xuejun Jiang, Li Zhang, Jianhao Du, Shuyi Duan, Xiaojian Zhang, Zifei Qin, Jing Yang, Kaisheng Liu, Baojian Wu
Summary: This study reveals that the intestinal clock plays a crucial role in regulating liver rhythmicity and metabolism. The loss of the intestinal clock leads to a large-scale reprogramming of the liver transcriptome and alters hepatic metabolism. The intestinal clock controls the rhythmicity of the hepatic transcription factor SREBP-1c, which further affects hepatic lipogenesis and gluconeogenesis. These findings suggest that targeting intestinal rhythms may be a new approach for improving metabolic health.
JOURNAL OF HEPATOLOGY
(2023)
Article
Oncology
Marc Pfefferle, Irina L. Dubach, Raphael M. Buzzi, Elena Duerst, Nadja Schulthess-Lutz, Livio Baselgia, Kerstin Hansen, Larissa Imhof, Sandra Koernig, Didier Le Roy, Thierry Roger, Rok Humar, Dominik J. Schaer, Florence Vallelian
Summary: The study revealed that CD40 signaling in Clec4f(+) Kupffer cells triggers anti-CD40 antibody-induced liver toxicity. However, controlled erythrophagocytosis and the linked anti-inflammatory signaling by the endogenous metabolite heme can be exploited to reprogram liver macrophages and prevent necroinflammatory liver disease caused by high-dose administration of anti-CD40 antibodies.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Immunology
Vijay Kumar, John H. Stewart IV
Summary: Molecular carcinogenesis is a complex process involving abnormalities in key biological processes. The six hallmarks of cancer illustrate its complexity, including self-sufficient growth signals, apoptosis resistance, antigrowth signal resistance, neo-angiogenesis, invasion/spread, and limitless replicative potential. Chronic inflammation leads to immune cell metabolism dysregulation and cancer progression. This article highlights immunometabolic reprogramming as a critical hallmark of cancer and suggests targeting it for novel immunotherapeutic approaches.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Gastroenterology & Hepatology
Chunyan Liu, Lintao Wang, Mengzhen Xu, Yajie Sun, Zhen Xing, Junfeng Zhang, Chunming Wang, Lei Dong
Summary: This study successfully transformed the spleen into a liver-like organ by directly reprogramming the splenic fibroblasts into hepatocytes. This method, which does not require cell or tissue transplantation, provides a potential therapeutic approach for the treatment of end-stage liver diseases.
Review
Oncology
Fahim Ahmad, Murali Krishna Cherukuri, Peter L. Choyke
Summary: While low-risk localized prostate cancer has a good prognosis with effective treatments, metastatic prostate cancer remains incurable and treatment resistance is a major issue. Resistance is primarily driven by tumor heterogeneity, altered genetic signatures, and metabolic reprogramming enabling tumors to adapt to drugs. Understanding prostate cancer metabolism may offer insights into therapy-induced adaptive responses and more durable therapeutic outcomes.
BRITISH JOURNAL OF CANCER
(2021)
Article
Chemistry, Multidisciplinary
Ting Wang, Fangzhou Sun, Chunxiao Li, Peng Nan, Yan Song, Xuhao Wan, Hongnan Mo, Jinsong Wang, Yantong Zhou, Yuzheng Guo, Aya Ei Helali, Dongkui Xu, Qimin Zhan, Fei Ma, Haili Qian
Summary: Liver metastasis is the most fatal event of colon cancer patients. The study identifies MTA1 as a new ATP synthase modulator that facilitates colon cancer liver metastasis by driving mitochondrial bioenergetic metabolism reprogramming and enhancing oxidative phosphorylation. MTA1 knockout increases the sensitivity of colon cancer to mitochondrial bioenergetic metabolism-targeted drugs and mTOR inhibitors, and inhibiting ATP5A enhances the sensitivity of liver-metastasized colon cancer to sirolimus in an MTA1-dependent manner.
Article
Gastroenterology & Hepatology
Cerise Yuen-Ki Chan, Vincent Wai-Hin Yuen, David Kung-Chun Chiu, Chi-Ching Goh, Kelsie L. Thu, David W. Cescon, Isabel Soria-Bretones, Cheuk-Ting Law, Jacinth Wing-Sum Cheu, Derek Lee, Aki Pui-Wah Tse, Kel Vin Tan, Misty Shuo Zhang, Bowie Po-Yee Wong, Chun-Ming Wong, Pek-Lan Khong, Irene Oi-Lin Ng, Mark R. Bray, Tak Wah Mak, Thomas Chung-Cheung Yau, Carmen Chak-Lui Wong
Summary: This study found that targeting the centrosome regulator PLK4 to activate the cytosolic DNA sensing-mediated immune response effectively suppressed tumor progression in late-stage mouse HCC through cell cycle inhibition and induction of antitumor immunity, presenting a durable suppressive effect.
Article
Gastroenterology & Hepatology
Vincent Wai-Hin Yuen, David Kung-Chun Chiu, Cheuk-Ting Law, Jacinth Wing-Sum Cheu, Cerise Yuen-Ki Chan, Bowie Po-Yee Wong, Chi-Ching Goh, Misty Shuo Zhang, Helen Do-Gai Xue, Aki Pui-Wah Tse, Yan Zhang, Henry Yee-Hin Lau, Derek Lee, Rex K. H. Au-Yeung, Chun-Ming Wong, Carmen Chak-Lui
Summary: This study aims to investigate how genetic composition and specific oncogenic pathways regulate the immune composition of hepatocellular carcinoma (HCC) and affect the response to immune checkpoint inhibitors (ICIs). By establishing mouse models with genetic genotypes similar to human HCCs using genome-editing techniques, the researchers found that "hot tumors" driven by genetic mutations responded well to anti-PD-1 treatment, while "cold tumors" did not. In addition, they discovered that the TKI sorafenib can enhance the sensitivity of "cold tumors" caused by certain genetic mutations to anti-PD-1 treatment.
JOURNAL OF HEPATOLOGY
(2023)
Review
Cell Biology
Tina Suoangbaji, Vanilla Xin Zhang, Irene Oi-Lin Ng, Daniel Wai-Hung Ho
Summary: Primary liver cancer (PLC), including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, is a major cause of cancer-related deaths worldwide. Surgical resection and liver transplantation are curative therapies for PLC, but many cases are inoperable and have a high rate of recurrence. Mouse models and single-cell RNA sequencing have played crucial roles in understanding PLC and identifying potential targets for treatment. This review summarizes recent studies that used these approaches, focusing on cellular and molecular components, and discusses the potential insights they can provide.
Article
Gastroenterology & Hepatology
Yi Xu, Yue Yao, Liang Yu, Hiu Ling Fung, Alexander Hin Ning Tang, Irene Oi-Lin Ng, Melody Y. M. Wong, Chi-Ming Che, Jing Ping Yun, Yunfu Cui, Judy Wai Ping Yam
Summary: This study reveals the role of CLTA in the uptake of sEVs to promote HCC progression. CLTA is overexpressed in tumor tissues compared to non-tumorous liver tissues and increases progressively with tumor stage. CLTA contributes to sEV uptake in cells, leading to enhanced cancerous properties of HCC. Mechanistically, CLTA increases CAPG expression to facilitate sEV uptake, thereby promoting proliferation, motility, and invasiveness of HCC cells. Additionally, the CLTA inhibitor Pitstop 2 alone or in combination with sorafenib attenuated tumor growth in mice implanted with PDXs.
HEPATOLOGY INTERNATIONAL
(2023)
Article
Multidisciplinary Sciences
Jacinth Wing-Sum Cheu, David Kung-Chun Chiu, Kenneth Kin-Leung Kwan, Chunxue Yang, Vincent Wai-Hin Yuen, Chi Ching Goh, Noreen Nog-Qin Chui, Wei Shen, Cheuk-Ting Law, Qidong Li, Misty Shuo Zhang, Macus Hao-Ran Bao, Bowie Po -Yee Wong, Cerise Yuen-Ki Chan, Cindy Xinqi Liu, Grace Fu -Wan Sit, Zher Yee Ooi, Haijing Deng, Aki Pui-Wah Tse, Irene Oi-Lin Ng, Carmen Chak-Lui Wong
Summary: Hypoxia-induced adenosine creates an immunosuppressive tumor microenvironment (TME) and dampens the efficacy of immune checkpoint inhibitors (ICIs). HIF-1 orchestrates adenosine efflux through activation of MXI1 and equilibrative nucleoside transporter 4, leading to adenosine accumulation in cancer cells and elevated extracellular adenosine levels. The immunosuppressive role of adenosine on immune cells was confirmed in vitro assays, and therapeutic combination of adenosine receptor antagonists and anti-PD-1 prolonged survival of HCC-bearing mice. This study highlights the importance of targeting adenosine in overcoming immune resistance in HCC.
Article
Medicine, General & Internal
Philip C. Haycock, Maria Carolina Borges, Kimberley Burrows, Rozenn N. Lemaitre, Stephen Burgess, Nikhil K. Khankari, Konstantinos K. Tsilidis, Tom R. Gaunt, Gibran Hemani, Jie Zheng, Therese Truong, Brenda M. Birmann, Tracy OMara, Amanda B. Spurdle, Mark M. Iles, Matthew H. Law, Susan L. Slager, Fatemeh Saberi Hosnijeh, Daniela Mariosa, Michelle Cotterchio, James R. Cerhan, Ulrike Peters, Stefan Enroth, Puya Gharahkhani, Loic Le Marchand, Ann C. Williams, Robert C. Block, Christopher I. Amos, Rayjean J. Hung, Wei Zheng, Marc J. Gunter, George Davey Smith, Caroline Relton, Richard M. Martin
Summary: Using Mendelian randomization, this study found that polyunsaturated fatty acids (PUFAs) may be causally related to colorectal cancer and esophageal squamous cell carcinoma, but they also increase the risk of inflammatory bowel disease.
Article
Pathology
Kristy Kwan-Shuen Chan, Kwan-Yung Au, Long-Hin Suen, Bernice Leung, Cheuk-Yan Wong, Wei-Qiang Leow, Tony Kiat-Hon Lim, Irene Oi-Lin Ng, Clive Yik-Sham Chung, Regina Cheuk-Lam Loz
Summary: The study reveals the functional role of sortilin in hepatocarcinogenesis by modulating the cancer secretome and deregulated lipid metabolism.
AMERICAN JOURNAL OF PATHOLOGY
(2023)
Article
Gastroenterology & Hepatology
Hongyang Huang, Yu-Man Tsui, Daniel Wai-Hung Ho, Clive Yik-Sham Chung, Karen Man-Fong Sze, Eva Lee, Gary Cheuk-Hang Cheung, Vanilla Xin Zhang, Xia Wang, Xueying Lyu, Irene Oi-Lin Ng
Summary: This study identified LANCL1 as a key cell surface protein that promotes HCC tumor initiation. LANCL1 stabilizes FAM49B to suppress ROS production and promote HCC tumorigenicity. Clinically, high co-expression of LANCL1 and FAM49B is associated with more advanced tumor stage and poorer prognosis in HCC.
Article
Chemistry, Multidisciplinary
Samuel Wan Ki Wong, Sze Keong Tey, Xiaowen Mao, Hiu Ling Fung, Zhi-Jie Xiao, Danny Ka Ho Wong, Lung-Yi Mak, Man-Fung Yuen, Irene Oi-Lin Ng, Jing Ping Yun, Yi Gao, Judy Wai Ping Yam
Summary: Hepatocellular carcinoma (HCC) growth and dissemination are driven by tumor-derived small extracellular vesicles (sEVs) and the upregulation of von Willibrand factor (vWF) along HCC stages. Elevated sEV-vWF levels promote angiogenesis, tumor-endothelial adhesion, pulmonary vascular leakiness, and metastasis in late-stage HCC patients. sEV-vWF modulates endothelial cells through increased VEGF-A and FGF2 levels, with FGF2 stimulating a positive feedback response in HCC via the FGFR4/ERK1 signaling pathway. Blocking tumor-endothelial intercellular communication through anti-vWF antibody or FGFR inhibitor improves the treatment outcome of sorafenib in a patient-derived xenograft mouse model, suggesting a new therapeutic strategy.
Article
Gastroenterology & Hepatology
Charles Shing Kam, Daniel Wai-Hung Ho, Vanessa Sheung-In Ming, Lu Tian, Karen Man-Fong Sze, Vanilla Xin Zhang, Yu-Man Tsui, Abdullah Husain, Joyce Man-Fong Lee, Carmen Chak-Lui Wong, Albert Chi-Yan Chan, Tan-To Cheung, Lo-Kong Chan, Irene Oi-Lin Ng
Summary: The up-regulation of PFKFB4 expression is associated with more aggressive tumor behavior in hepatocellular carcinoma (HCC) and plays a critical role in HCC development, with therapeutic implications.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Gastroenterology & Hepatology
Martina Mang Leng Lei, Carmen Oi Ning Leung, Eunice Yuen Ting Lau, Rainbow Wing Hei Leung, Victor Wan San Ma, Man Tong, Yin Ying Lu, Chen Yang Huang, Qiao Hua Zhu, Irene Oi Lin Ng, Stephanie Ma, Terence Kin Wah Lee
Summary: This study reveals that SCYL3 plays a critical role in promoting the progression of hepatocellular carcinoma (HCC). It is often overexpressed in HCC, especially in metastatic tumors, and is associated with worse patient survival. Suppression of SCYL3 attenuates cell proliferation, migration, and in vivo metastasis in HCC.
Article
Gastroenterology & Hepatology
Jacinth Wing-Sum Cheu, Derek Lee, Qidong Li, Chi Ching Goh, Macus Hao-Ran Bao, Vincent Wai-Hin Yuen, Misty Shuo Zhang, Chunxue Yang, Cerise Yuen-Ki Chan, Aki Pui-Wah Tse, Grace Fu-Wan Sit, Cindy Xinqi Liu, Irene Oi-Lin Ng, Chun-Ming Wong, Carmen Chak-Lui Wong
Summary: This study identified FSP1 as a potential therapeutic target for hepatocellular carcinoma (HCC). Inhibiting FSP1 induced ferroptosis, enhanced the anti-tumor immune response, and effectively suppressed HCC tumor growth. FSP1 inhibition represents a new therapeutic strategy for HCC.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)