Article
Oncology
Kai-Yen Peng, Shih-Sheng Jiang, Yu-Wei Lee, Fang-Yu Tsai, Chia-Chi Chang, Li-Tzong Chen, B. Linju Yen
Summary: Research found that stromal-secreted Gal-1 promotes CIC-features and disease dissemination in CRC through SOX9 and beta-catenin, with Gal-1 and SOX9 having a strong clinical prognostic value.
FRONTIERS IN ONCOLOGY
(2021)
Editorial Material
Biochemistry & Molecular Biology
Alessa L. Henneberg, Christiane A. Opitz
Summary: A recent study has revealed that hepatocellular carcinoma cells suppress the urea cycle enzymes and depend on the uptake of exogenous arginine and GCN2 kinase-induced cell-cycle arrest for survival. These findings present new possibilities for combination therapy in liver cancer.
Article
Oncology
Jae-Il Choi, Sung Ill Jang, Jaehyun Hong, Chul Hoon Kim, Soon Sung Kwon, Joon Seong Park, Jong-Baeck Lim
Summary: In this study, it was demonstrated that CD44(+), CD24(+) and EpCAM(+) cancer-initiating cells (CICs) were enriched in patient-derived organoids of PDAC. CD44-expressing CICs formed lumen structures within the organoids. Additionally, CD44(-) cancer cells from the organoids could re-form organoids and be re-programed as CD44-expressing CICs. The study also showed that the maintenance of CICs in PDAC organoids was mediated by interactions with endothelial cells through Wnt and Notch signaling pathways.
Article
Multidisciplinary Sciences
C. Megan Young, Laurent Beziaud, Pierre Dessen, Angela Madurga Alonso, Albert Santamaria-Martinez, Joerg Huelsken
Summary: This study examines the metabolic adaptations of metastasis-initiating cells (MICs) in female breast cancer and how those shape their metastatic phenotype. The findings demonstrate that MICs specifically alter their metabolism to efficiently colonize distant organs, and understanding these mechanisms may help control cancer progression.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Masaya Yamazaki, Shinjiro Hino, Shingo Usuki, Yoshihiro Miyazaki, Tatsuya Oda, Mitsuyoshi Nakao, Takaaki Ito, Kazuya Yamagata
Summary: Tumor-initiating cells with high expression of receptor tyrosine kinase-like orphan receptor 1 (ROR1) have partial epithelial-mesenchymal transition (EMT)-like signature and act as the origin of heterogeneous tumor cells in PDAC. ROR1 depletion suppresses tumor growth, recurrence after chemotherapy, and metastasis by inducing the expression of Aurora kinase B (AURKB) through activating E2F via c-Myc. ROR1 is transcriptionally dependent on YAP/BRD4 binding at the enhancer region and targeting this pathway reduces ROR1 expression and prevents PDAC growth.
Article
Biochemistry & Molecular Biology
Jun Li, Xingyang Zhong, Xinjun Wang, Feng Xu, Jiamei Yang, Junhua Lu, Caifeng Liu, Jiongjiong Lu
Summary: MiR-93 is highly expressed in liver T-ICs, enhancing their self-renewal and tumorigenesis abilities by regulating MTMR3 and contributing to drug resistance. Patients with low miR-93 levels benefit more from TACE or sorafenib treatment in HCC cases.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Review
Oncology
Keigo Machida, Stanley M. Tahara
Summary: This review discusses the pharmacological and immune therapeutic targeting for hepatocellular carcinoma (HCC) and cholangiocarcinoma, as well as the role of immunotherapies and microbiota in tumor-initiating stem-like cells (TICs). Gut dysbiosis inhibits the efficacy of immunotherapies, and personalized medicine approaches targeting TIC/metastasis-initiating cells may be potential targets for HCC immunotherapy and microbiota modulation therapy.
Article
Oncology
Brittney S. Harrington, Rahul Kamdar, Franklin Ning, Soumya Korrapati, Michael W. Caminear, Lidia F. Hernandez, Donna Butcher, Elijah F. Edmondson, Nadia Traficante, Joy Hendley, Madeline Australian Ovarian Canc Study, Madeline Gough, Rebecca Rogers, Rohan Lourie, Jyoti Shetty, Bao Tran, Fathi Elloumi, Abdalla Abdelmaksoud, Madhu Lal Nag, Krystyna Mazan-Mamczarz, Carrie D. House, John D. Hooper, Christina M. Annunziata
Summary: The study found that UGDH plays distinct roles in different molecular subtypes of epithelial ovarian cancer, influencing the tumor microenvironmental composition. UGDH is a strong potential therapeutic target in TICs, particularly in patients with the mesenchymal molecular subtype of EOC.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Shuping Qu, Xiaobing Zhang, Yue Wu, HengYu Li, Jian Zhai, Dong Wu
Summary: Evidence suggests that miR-361-3p plays a crucial role in the expansion of liver tumor-initiating cells (T-ICs) and their response to TACE or sorafenib treatment. Upregulation of miR-361-3p enhances self-renewal and tumorigenicity of liver T-ICs, while knockdown of miR-361-3p impairs these abilities. Furthermore, miR-361-3p directly targets SOX1 in liver T-ICs, revealing its potential as a therapeutic target for the prevention and intervention in HCC.
Article
Oncology
Miaoling Tang, Meisongzhu Yang, Geyan Wu, Shuang Mo, Xingui Wu, Shuxia Zhang, Ruyuan Yu, Yameng Hu, Yingru Xu, Ziwen Li, Xinyi Liao, Jun Li, Libing Song
Summary: In liver cancer cells, the upregulation of MFF mediated by the TBX19/PRMT1 complex promotes mitochondrial fission and tumor-initiating capacity, indicating that PRMT1 may be a viable therapeutic target in liver cancer.
Article
Nanoscience & Nanotechnology
Priya Dharmalingam, Krishnan Venkatakrishnan, Bo Tan
Summary: This study developed a multimode nanoplatform to investigate epigenetic changes in tumor-initiating cancer stem cells and explore their transformation signals following drug therapy. By utilizing surface-enhanced Raman scattering technology and dopant functionalization, biomarkers in tiCSCs can be analyzed label-free at the cellular level.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Oncology
Michael W. Caminear, Brittney S. Harrington, Rahul D. Kamdar, Michael J. Kruhlak, Christina M. Annunziata
Summary: The study found that disulfiram was more effective in reducing the viability of TICs compared to NCTs, affecting NF kappa B signaling, and was more suitable as a therapeutic to prevent EOC relapse.
FRONTIERS IN ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Valentin J. A. Barthet, Martina Brucoli, Marcus J. G. W. Ladds, Christoph Nossing, Christos Kiourtis, Alice D. Baudot, James O'Prey, Barbara Zunino, Miryam Muller, Stephanie May, Colin Nixon, Jaclyn S. Long, Thomas G. Bird, Kevin M. Ryan
Summary: The study presents a genetically engineered mouse model of HCC driven by loss of autophagy and hemizygosity of PTEN, showing the involvement of ductular reaction in HCC development. Following loss of autophagy, mature hepatocytes dedifferentiate into biliary-like liver progenitor cells, leading to HCC. Deletion of YAP and TAZ transcription factors reverses the dedifferentiation and tumorigenesis, suggesting new potential targets for therapeutic intervention.
Article
Biochemistry & Molecular Biology
Yang Gu, Yanying Wang, Luyun He, Jiahang Zhang, Xiaoxiao Zhu, Nian Liu, Jianyi Wang, Tiankun Lu, Lei He, Yong Tian, Zusen Fan
Summary: This study identified circIPO11 as highly expressed in HCC tumor tissues and liver CSCs, playing a critical role in self-renewal maintenance of liver CSCs and HCC development. Mechanistically, circIPO11 activates the Hedgehog signaling pathway, promoting tumor cell propagation. Targeting circIPO11 and the Hedgehog pathway may provide new potential for HCC treatment.
Article
Oncology
Mikella Robinson, Samuel F. Gilbert, Jennifer A. Waters, Omar Lujano-Olazaba, Jacqueline Lara, Logan J. Alexander, Samuel E. Green, Gregory A. Burkeen, Omid Patrus, Zinia Sarwar, Ryne Holmberg, Christine Wang, Carrie D. House
Summary: The findings suggest that SOX2 may be a more consistent indicator of ovarian tumor initiating cells (TICs) that contribute to tumor repopulation following chemotherapy. Further studies evaluating SOX2 in TIC biology will enhance understanding of mechanisms driving ovarian cancer relapse.
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
Xia Wang, Hongyang Huang, Karen Man-Fong Sze, Jin Wang, Lu Tian, Jingyi Lu, Yu-Man Tsui, Hoi Tang Ma, Eva Lee, Ao Chen, Joyce Lee, Ying Wang, Judy Wai Ping Yam, Tan-To Cheung, Xinyuan Guan, Irene Oi-Lin Ng
Summary: The study found that S100A10 plays an important role in the progression of HCC by transferring in extracellular vesicles (EV-S100A10) and regulating the protein cargoes of EVs. EV-S100A10 may be a potential therapeutic target and biomarker for HCC progression.
Article
Gastroenterology & Hepatology
Yung-Tuen Chiu, Abdullah Husain, Karen Man-Fong Sze, Daniel Wai-Hung Ho, Eliana Mary Senires Suarez, Xia Wang, Eva Lee, Hoi-Tang Ma, Joyce Man-Fong Lee, Lo-Kong Chan, Irene Oi-Lin Ng
Summary: This study identified Mid-line 1 interacting protein 1 (MID1IP1) as a key gene in the metastasis of hepatocellular carcinoma (HCC). It was found that MID1IP1 promoted HCC migration and invasion by upregulating FOS like 1 (FRA1) and subsequently activating MMP9 signaling. Targeting the MID1IP1-mediated FRA1 pathway may be a potential therapeutic strategy against HCC progression.
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
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
Cell Biology
Xiaozhe Zhang, Gao Shan, Na Li, Jingyi Chen, Changyang Ji, Xiaoxiao Li, Liwen Jiang, Terence Kin Wah Lee, Vincent W. Keng, Yanxiang Zhao
Summary: TNBC is an aggressive subtype of breast cancer with autophagy defect. A peptide called Tat-SP4 was developed to induce autophagy and promote endolysosomal trafficking in TNBC cells, leading to autosis cell death and inhibition of cell proliferation.
CELL DEATH DISCOVERY
(2023)
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)
