Article
Biochemistry & Molecular Biology
Richard Huang, Jalna Meens, Scott Yuzwa, Laurie Ailles, Michael Ohh, Claire M. Robinson
Summary: Cancer stem cells play an important role in tumor biology. This study aimed to identify the existence of clear cell renal cell carcinoma (ccRCC) stem cells using the side population approach, but the results did not support the presence of cancer stem cells in ccRCC.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Cell Biology
Fangfang Wang, Zhang Dan, Hongmei Luo, Jingcao Huang, Yushan Cui, Hong Ding, Juan Xu, Zhimei Lin, Yuhan Gao, Xinyu Zhai, Yan Yang, Ying Qu, Li Zhang, Fengjiao Chen, Qiang Wang, Xin Wang, Yu Feng, Ting Liu, Qing Yi, Ting Niu, Yuhuan Zheng
Summary: Drug-resistance is a major problem in multiple myeloma (MM) patients. This study reveals that activated-leukocyte-cell-adhesion-molecule (ALCAM) regulates MM side population (SP)-mediated drug-resistance through the ALCAM-EGF/EGFR axis. EGFR activation promotes the SP ratio, while ALCAM inhibits EGFR downstream signaling in MM cells. SP MM cells have a higher number of mitochondria and interference of mitochondrial function inhibits SP-genesis. Combination therapy with an anti-MM agent and EGFR inhibitor gefitinib improves MM therapeutic efficacy and prolongs survival in MM-bearing mice.
CELL DEATH & DISEASE
(2022)
Article
Multidisciplinary Sciences
Xiaoli Dong, Yingying Wei, Tao Xu, Xiaoyue Tan, Na Li
Summary: Cancer stem cells (CSCs) play a crucial role in tumor growth, metastasis, and recurrence. Techniques such as staining tumor cells with Hoechst 33342 and analyzing the proportion of side population (SP) cells using flow cytometry provide convenient, fast, and cost-effective methods for the identification and purification of CSCs. Data generated from these assays can contribute to a better understanding of the stemness properties of tumor cells in response to various signals.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2021)
Article
Oncology
Wen Jing, Mao Zhou, Ruixia Chen, Xijiu Ye, Weixing Li, Xiangfei Su, Jianwei Luo, Zhi Wang, Shuling Peng
Summary: Targeting ABCG2 with tucatinib can sensitize ABCG2-overexpressing leukemia cells and LSCs to conventional chemotherapeutic agents by blocking ABCG2 pump function, thereby enhancing the efficacy of leukemia therapy.
Article
Multidisciplinary Sciences
Jiajia Xu, Zhao Li, Robert J. Tower, Stefano Negri, Yiyun Wang, Carolyn A. Meyers, Takashi Sono, Qizhi Qin, Amy Lu, Xin Xing, Edward F. McCarthy, Thomas L. Clemens, Aaron W. James
Summary: Bone regeneration following injury is coordinated by inflammatory signals and sensory nerve infiltration. This study demonstrates that nerve growth factor (NGF) signals through p75 to affect migration of mesenchymal osteogenic precursors, thereby impacting bone healing. Lack of NGF or p75 results in delayed bone repair.
Article
Cell Biology
Xi Xu, Wenwen Zhang, Li Xuan, Yanhui Yu, Wen Zheng, Fang Tao, Jacqelyn Nemechek, Chong He, Weiwei Ma, Xue Han, Siyu Xie, Minyi Zhao, Jian Wang, Yuhua Qu, Qifa Liu, John M. Perry, Linjia Jiang, Meng Zhao
Summary: “T cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy. In this study, a rare inhibitory receptor called programmed cell death 1 (PD-1) was identified as a marker for leukemia stem cells (LSCs) in T-ALL. Blocking PD-1 significantly eradicated LSCs and suppressed disease progression, and combination therapy with PD-1 blockade and chemotherapy extended survival. Mechanistically, PD-1+ LSCs had high NOTCH1-MYC activity and were protected against apoptosis. These findings provide a therapeutic approach for eliminating LSCs in T-ALL.”
NATURE CELL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Katie A. Fennell, Dane Vassiliadis, Enid Y. N. Lam, Luciano G. Martelotto, Jesse J. Balic, Sebastian Hollizeck, Tom S. Weber, Timothy Semple, Qing Wang, Denise C. Miles, Laura MacPherson, Yih-Chih Chan, Andrew A. Guirguis, Lev M. Kats, Emily S. Wong, Sarah-Jane Dawson, Shalin H. Naik, Mark A. Dawson
Summary: Studies have shown that malignant clonal dominance is a cell-intrinsic and heritable property facilitated by the repression of antigen presentation and increased expression of the secretory leukocyte peptidase inhibitor gene (Slpi). Increased transcriptional heterogeneity enables clonal fitness in diverse tissues and immune microenvironments, as well as in the context of clonal competition between genetically distinct clones. Leukemia stem cells (LSCs) display heritable clone-intrinsic properties of high and low clonal output, which contribute to the overall tumor mass.
Article
Pharmacology & Pharmacy
Xiaojiang Liu, Yiqiu Cui, Jun Li, Cheng Guan, Shu Cai, Jinrong Ding, Jianhong Shen, Yixiang Guan
Summary: PTEN inhibitor bpv(pic) promotes the proliferation and differentiation of NSCs into neurons by regulating the expression and phosphorylation of the Akt/mTOR signaling pathway.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Daniela Damiani, Mario Tiribelli
Summary: The prognosis of acute myeloid leukemia (AML) remains unsatisfactory due to poor response to therapy or relapse, which can be attributed to the over-expression of multidrug resistance (MDR) proteins. ABCG2, an efflux transporter responsible for inducing MDR in leukemic cells, has the ability to extrude many antineoplastic drugs, leading to AML resistance and/or relapse. This review focuses on the expression and role of ABCG2, as well as its regulation and potential inhibition to counteract drug resistance and improve outcomes in AML patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Angela Russo, Jose A. Colina, Junlone Moy, Seth Baligod, Austin A. Czarnecki, Peter Varughese, Daniel D. Lantvit, Matthew J. Dean, Joanna E. Burdette
Summary: Loss of PTEN in FTE leads to enrichment of cancer stem cell markers and altered cell function, while loss of PAX2 plays a crucial role in this process. Additionally, PTEN loss generates two distinct subpopulations of cells with different cancer stem-like cell marker expression and chemoresistance profiles.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Rachid Lahlil, Anne Aries, Maurice Scrofani, Celine Zanetti, Desline Hennequin, Bernard Drenou
Summary: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disease characterized by the presence of the BCR-ABL fusion gene. Treatment with tyrosine kinase inhibitors (TKIs) such as imatinib mesylate (IM) has significantly improved clinical outcomes for CML patients, but IM resistance remains a major challenge. The cause of IM resistance in CML cells is unclear, but additional genetic alterations in leukemic stem cells (LSCs) are a common cause of relapse. A study found that a rare subpopulation of stem cells called very small embryonic-like stem cells (VSELs) in adult CML patients is resistant to IM and less sensitive to apoptosis compared to leukemic hematopoietic stem cells (HSCs). The expression levels of certain miRNAs are also affected in these IM-resistant VSELs, including miR-126 and miR-21, which are involved in LSC leukemia-initiating capacity and growth.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Gisel Bares, Aida Bea, Luis Hernandez, Raul Navaridas, Isidre Felip, Cristina Megino, Natividad Blasco, Ferran Nadeu, Elias Campo, Marta Llovera, Xavier Dolcet, Daniel Sanchis
Summary: The PI3K/AKT pathway plays a crucial role in cell survival and proliferation in various cancer types. Silencing of the ENDOG gene can inhibit cancer cell proliferation and serve as a prognostic marker in specific cancer types.
Review
Cell Biology
Peipei Wang, Mengdie Feng, Guoqiang Han, Rong Yin, Yashu Li, Shuxin Yao, Pengbo Lu, Yuhua Wang, Haojian Zhang
Summary: This review summarizes the importance of N-6-methyladenosine modification in maintaining normal hematopoietic stem cell function and leukemia pathogenesis, highlighting the roles of m(6)A writers, readers, and erasers. Mechanisms of m(6)A modifiers in preserving the function of hematopoietic stem cells and leukemia stem cells are discussed, along with potential strategies for targeting m(6)A modification related pathways.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Sofia Nikouli, Mary Tsikitis, Christina Raftopoulou, Sarantis Gagos, Stelios Psarras, Yassemi Capetanaki
Summary: The limited regenerative capacity of the heart has led to the need for new stem cell-based therapeutic approaches for cardiac regeneration. However, the use of stem cells is restricted due to poor determination of their properties and regulatory factors. In this study, the role of desmin, a major muscle-specific intermediate filament protein, in the characteristics and differentiation capacity of adult mouse cardiac side population (CSP) and Sca1(+) stem cells was investigated. It was found that desmin deficiency affects the microenvironment of the cells and impairs their regenerative potential, both directly and indirectly.
CELL AND TISSUE RESEARCH
(2022)
Article
Cell Biology
Qiaoyi Sun, Li Ma, Jing Qiao, Xing Wang, Jianguo Li, Yuxi Wang, Ailing Tan, Zihui Ye, Yukang Wu, Jiajie Xi, Jiuhong Kang
Summary: The expression level of miR-181a-5p was found to be decreased in the hippocampal NSCs of aged mice, and exogenous overexpression of miR-181a-5p promoted NSC proliferation and improved learning and memory impairments caused by aging. The mechanistic study revealed that miR-181a-5p targeted phosphatase and tensin homolog (PTEN), a negative regulator of the AKT signaling pathway, and knockdown of PTEN rescued the impairment of NSC proliferation by low miR-181a-5p levels. Furthermore, overexpression of miR-181a-5p in the dentate gyrus increased NSC proliferation and ameliorated learning and memory impairments in aged mice.
Review
Oncology
Xinru Zhou, Yin Jia, Chuanbin Mao, Shanrong Liu
Summary: Small extracellular vesicles (sEVs), such as exosomes, have emerged as crucial targets for liquid biopsy and promising drug delivery vehicles in tumor progression. They can serve as biomarkers for tumor diagnosis and as drug carriers for cancer treatment.
Article
Oncology
Ruochan Chen, Ju Zhu, Xiao Zhong, Jie Li, Rui Kang, Daolin Tang
Summary: The interplay between autophagy and apoptosis plays a crucial role in tumorigenesis and cancer therapy, with HMGB1 serving as a key regulator in these processes.
Article
Oncology
Zongfu Pan, Xixuan Lu, Tong Xu, Jinming Chen, Lisha Bao, Ying Li, Yingying Gong, Yulu Che, Xiaozhou Zou, Zhuo Tan, Ping Huang, Minghua Ge
Summary: This study uncovered the emerging role of HN1 in promoting dedifferentiation of anaplastic thyroid cancer (ATC) cells. HN1 negatively regulated the thyroid differentiation markers and had an inhibitory effect on the transcriptional activation of CTCF, thereby influencing the chromatin accessibility of thyroid differentiation genes.
Article
Oncology
Yi Qin, Shengjun Xiong, Jun Ren, Gautam Sethi
Summary: Autophagy plays an important regulatory role in glioblastoma, and its dysregulation can lead to drug resistance and radioresistance. It also affects stem cell characteristics, overall growth, and metastasis. Therefore, autophagy is a promising target for glioblastoma therapy.
Article
Oncology
Katsuya Nagaoka, Xuewei Bai, Dan Liu, Kevin Cao, Joud Mulla, Chengcheng Ji, Hongze Chen, Muhammad Azhar Nisar, Amalia Bay, William Mueller, Grace Hildebrand, Jin-Song Gao, Shaolei Lu, Hiroko Setoyama, Yasuhito Tanaka, Jack R. Wands, Chiung-Kuei Huang
Summary: This study found that serum 2-OG levels in cholangiocarcinoma patients are associated with the effectiveness of chemotherapy. Patients with progressive disease showed significantly higher levels of serum 2-OG compared to stable disease and partial response patients. The study also revealed that overexpression of ASPH mimics the effects of 2-OG, and knockdown of ASPH improves chemotherapy. Targeting ASPH enhances the effects of chemotherapy by modulating ATM and ATR, two key regulators of DDRs.
