Review
Biochemistry & Molecular Biology
Martin Snajdauf, Klara Havlova, Jiri Vachtenheim, Andrej Ozaniak, Robert Lischke, Jirina Bartunkova, Daniel Smrz, Zuzana Strizova
Summary: TRAIL, as a potential target for cancer therapy, has limitations in human applications despite promising preclinical observations; to enhance the anti-tumor potential of TRAIL therapies, novel TRAIL derivatives and modifications have been designed, but most are still at preclinical stage; more clinical trials of TRAIL therapies may emerge in the future.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Cell Biology
Emir Bozkurt, Heiko Dussmann, Manuela Salvucci, Brenton L. Cavanagh, Sandra Van Schaeybroeck, Daniel B. Longley, Seamus J. Martin, Jochen H. M. Prehn
Summary: The study reveals that TRAIL signaling not only activates apoptosis in colon cancer cells but also induces entosis through TRAIL receptors and the structural presence of caspase-8. The association of TRAIL signaling with cell-in-cell structures is significant in colorectal cancer, especially in the context of patient prognosis. Factors controlling entosis in tumors remain to be elucidated despite the evidence of entosis in cancers.
JOURNAL OF CELL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Anderson Luiz-Ferreira, Teresa Pacifico, Alefe Cardoso Cruz, Federica Laudisi, Giovanni Monteleone, Carmine Stolfi
Summary: TRAIL is a promising anticancer agent that selectively induces apoptosis in transformed cells, while flavonoids, natural compounds found in plants, have shown competence in enhancing TRAIL-induced apoptosis. However, bioavailability issues are the main limitations for the clinical use of flavonoids.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Hannah J. Vaughan, Camila G. Zamboni, Nicholas P. Radant, Pranshu Bhardwaj, Esther Revai Lechtich, Laboni F. Hassan, Khalid Shah, Jordan J. Green
Summary: Researchers have developed poly(beta-amino ester) nanoparticles to locally deliver a secretable TRAIL protein to liver cancer cells, inducing apoptosis effectively. By combining NP treatment with histone deacetylase inhibitors, they achieved over 80% TRAIL-mediated cell death in target cancer cells. This approach offers a new potential strategy for cancer treatment by addressing multiple challenges associated with TRAIL therapy.
MOLECULAR THERAPY-ONCOLYTICS
(2021)
Article
Cell Biology
Ruisong Ding, Xingyou Hu, Wen Hu, Zhenzhen Du, Panpan Huang, Mengyang Wang, Jiaoyue Sheng, Yanchao Ma, Ailing Wang, Xiying Luan, Menghua Dong, Qizhi Cao, Yanfen Zou, Tao Hu
Summary: The study revealed that abnormal O-glycosylation caused by Cosmc mutations can lead to Tn antigen expression. Transfection of Cosmc resulted in reduced proliferation and migration of Tn(+) cells, along with increased sensitivity to apoptosis induced by Apo2L/TRAIL. Differences in O-glycan composition among various Tn(+) cells affect cell behavior and modulate sensitivity to apoptotic stimuli.
Review
Biochemistry & Molecular Biology
You-Take Oh, Shi-Yong Sun
Summary: The involvement of the TRAIL/death receptor signaling pathway in the regulation of cancer invasion and metastasis is complex, with both positive and negative roles reported. The underlying molecular mechanisms are even more complicated. This review focuses on discussing the current understanding of how TRAIL/death receptor-mediated signaling regulates cancer cell invasion and metastasis.
Article
Cell Biology
Oliver H. Voss, Daniel Arango, Justin C. Tossey, Miguel A. Villalona Calero, Andrea Doseff
Summary: Apigenin sensitizes primary lung cancer cells to TRAIL-induced apoptosis through reprogramming alternative splicing of key TRAIL/DISC components and directly binding heat shock protein 70 to promote cell death. These findings emphasize the synergies between diet and cancer treatments, providing new avenues for improved cancer therapies.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Anna-Christina Rambow, Insa Aschenbach, Sofie Hagelund, Doaa Tawfik, Jan-Paul Gundlach, Sebastian Weisse, Nicolai Maass, Anna Trauzold
Summary: Binding of TRAIL to its death domain-containing receptors TRAIL-R1 and TRAIL-R2 can induce cell death and/or pro-inflammatory signaling. The importance of TRAIL and TRAIL-R1/R2 in tumor immune surveillance and cancer biology has meanwhile been well documented. TRAIL also binds to TRAIL-R3 and TRAIL-R4, which have regulatory functions in apoptotic and non-apoptotic signaling pathways. Knockdown of TRAIL-R4 affects the activation of apoptotic and non-apoptotic pathways in cancer cells, showing opposing effects on cell death and clonogenic survival. TRAIL-R4 also regulates the expression of anti-apoptotic proteins and affects the activity of AKT, ERK, p38 and NF-kappa B. This study provides evidence for the important role of endogenous TRAIL-R4 in cancer cells and improves the understanding of the complex TRAIL/TRAIL-R system in humans.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
K. M. A. Zinnah, Sang-Youel Park
Summary: The study demonstrated the mechanism behind the synergistic anticancer effect of amitriptyline and TRAIL, showing that amitriptyline increases TRAIL-induced apoptosis by upregulating death receptors DR4 and DR5. Inhibition of autophagy by amitriptyline was also shown to enhance DR4 and DR5 expression.
Review
Oncology
Julio M. Pimentel, Jun-Ying Zhou, Gen Sheng Wu
Summary: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a promising agent for cancer therapy due to its selective induction of apoptosis in tumor cells without harming normal cells. However, the efficacy of TRAIL-based therapies in clinical trials is limited. In addition to its role in cancer cell apoptosis, TRAIL also plays a critical role in tumor immunosurveillance and may interact with immune checkpoint proteins, such as programmed death-ligand 1 (PD-L1), to modulate PD-L1-based tumor immunotherapies. This review discusses recent findings on TRAIL-based therapy, resistance, and its involvement in tumor immunosurveillance.
Article
Biochemistry & Molecular Biology
Manami Semba, Shinji Takamatsu, Sachiko Komazawa-Sakon, Eiji Miyoshi, Chiharu Nishiyama, Hiroyasu Nakano, Kenta Moriwaki
Summary: The study identified proscillaridin A as a promising agent that enhances the anti-cancer efficacy of TRAIL therapeutics, particularly in colon cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Qiang Zhou, Jianxia Yuan, Yi Liu, Yayun Wu
Summary: Cisatracurium besilate inhibits gastric cancer cell proliferation, promotes apoptosis, increases the expression of p53 and PUMA, and enhances TRAIL-induced apoptosis. However, pifithrin-alpha can reverse the synergistic effects of cisatracurium besilate and TRAIL on AGS cell activities.
Article
Oncology
Andrea Rizzo, Alessandro Satta, Giulia Garrone, Adalberto Cavalleri, Alessandra Napoli, Francesco Raspagliesi, Mariangela Figini, Loris De Cecco, Egidio Iorio, Antonella Tomassetti, Delia Mezzanzanica, Marina Bagnoli
Summary: The study showed that down-regulation of CHKA can enhance the sensitivity of OC cells to TRAIL-mediated apoptosis, resulting in increased expression of TRC and TRAIL-R2, regulation of TRAIL-R2 localization, and enhanced TRAIL-induced apoptotic signaling.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Tomoya Fukuoka, Kenta Moriwaki, Shinji Takamatsu, Jumpei Kondo, Miki Tanaka-Okamoto, Azusa Tomioka, Manami Semba, Sachiko Komazawa-Sakon, Yoshihiro Kamada, Hiroyuki Kaji, Yasuhide Miyamoto, Masahiro Inoue, Kazuhiko Bessho, Yoko Miyoshi, Keiichi Ozono, Hiroyasu Nakano, Eiji Miyoshi
Summary: The study reveals that Lewis glycans positively regulate TRAIL-induced cell death, providing important insights into TRAIL sensitivity. Moreover, the expression of type I Lewis glycans is positively correlated with TRAIL sensitivity in colon cancer cell lines and patient-derived cancer organoids.
Review
Oncology
Ammad Ahmad Farooqi, Rakhmetova Venera, Gulnara Kapanova, Gulnur Tanbayeva, Gulshara Akhmetova, Yerlan Kudabayev, Assiya Turgambayeva
Summary: Bladder cancer is a challenging disease, and researchers have made significant progress in understanding the mechanisms underlying its development and progression. Restoring apoptosis in drug-resistant cancers, particularly through TRAIL-mediated signaling, shows promise as a valuable treatment strategy. Various natural products and agonistic antibodies have been tested in clinical trials, demonstrating encouraging results in sensitizing drug-resistant bladder cancer cells to apoptosis. Multipronged approaches combining natural products, chemotherapeutics, and agonistic antibodies show potential in well-designed clinical trials.
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.