Article
Chemistry, Medicinal
Elena Puris, Sabrina Petralla, Seppo Auriola, Heidi Kidron, Gert Fricker, Mikko Gynther
Summary: Triple negative breast cancer (TNBC) is an aggressive and deadly subtype of cancer. Intra-tumoral hypoxia is associated with aggressiveness and drug resistance in TNBC, particularly through the elevated expression of efflux transporters like ABCG2. This study explores the possibility of reducing ABCG2-mediated drug resistance in hypoxic TNBC cells by inhibiting monoacylglycerol lipase (MAGL) and subsequently downregulating ABCG2 expression. The results demonstrate that MAGL inhibition effectively reduces ABCG2 expression, increases drug accumulation, and improves drug efficacy in TNBC cells.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Oncology
Xinyang Li, Xiang Yuan, Ziming Wang, Jing Li, Zhiwei Liu, Yukun Wang, Limin Wei, Yuanpei Li, Xinshuai Wang
Summary: This study demonstrates that the combination of chidamide and fluzoparib could reverse the resistance of TNBC cells to fluzoparib by reducing the expression levels of RAD51 and MRE11, two key drug resistance genes.
FRONTIERS IN ONCOLOGY
(2022)
Article
Pharmacology & Pharmacy
Yingqiang Fu, Wei Dong, Yuting Xu, Lin Li, Xin Yu, Yuheng Pang, Liujia Chan, Yuhan Deng, Cheng Qian
Summary: In this study, a three-dimensional (3D) cultured breast cancer stem cell spheres model was constructed to investigate the role of mitochondrial dynamics in BCSCs. The results showed that the protein levels of FIS1 and Mitofusin 1 were increased in BCSCs. Treatment with Capivasertib (AZD5363) suppressed Mitofusin 1 expression and induced apoptosis in BCSCs, making them more sensitive to Doxo.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Yong Weon Yi
Summary: Anticancer drug resistance is a major challenge in cancer treatment, and extracellular vesicles (EVs) derived from cancer cells have been identified as a crucial mechanism for drug resistance, tumor progression, and metastasis. EVs, which consist of a lipid bilayer, can transfer various substances including proteins, nucleic acids, lipids, and metabolites from the originating cell to the recipient cell. The investigation of EVs' role in drug resistance is still at an early stage. This review analyzes the involvement of EVs derived from triple-negative breast cancer cells (TNBC-EVs) in anticancer drug resistance and discusses strategies to overcome TNBC-EV-mediated drug resistance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Narjara Gonzalez Suarez, Yuniel Fernandez-Marrero, Mathieu P. A. Hebert, Marie-Eve Roy, Luc H. Boudreau, Borhane Annabi
Summary: This study aimed to investigate the regulatory effect of green tea polyphenol EGCG on extracellular vesicles (EVs) in triple-negative breast cancer cells' secretome. The research found that EGCG significantly modified the genetic material of EVs under low oxygen conditions, reduced the ability of cancer cells to induce inflammation in adipose-derived mesenchymal stem cells (hADMSC), and decreased the mitochondrial content in cancer cell-derived EVs.
CANCER CELL INTERNATIONAL
(2023)
Article
Chemistry, Medicinal
Rui He, Zhiqiang Song, Yu Bai, Sheng He, Jing Huang, Yongxing Wang, Fengtao Zhou, Weixue Huang, Jing Guo, Zhen Wang, Zheng-Chao Tu, Xiaomei Ren, Zhang Zhang, Jian Xu, Ke Ding
Summary: AXL kinase is crucially involved in cancer tumorigenesis, metastasis, and drug resistance, and multiple AXL inhibitors are currently being investigated in clinical trials. Recent research has highlighted the importance of the N-terminal region of AXL in cell invasiveness, suggesting that targeting AXL degradation could be a more effective therapeutic approach compared to kinase inhibitors. In this study, a series of new AXL PROTAC degraders were discovered, with compound 6n emerging as a potent AXL depletor in TNBC cells. It exhibited superior inhibitory effects on AXL signaling activation, cell proliferation, migration, and invasion compared to the corresponding kinase inhibitor. Additionally, compound 6n showed promising therapeutic potential in patient-derived organoids and a mouse model of MDA-MB-231 cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Jiawen Bu, Yixiao Zhang, Sijin Wu, Haonan Li, Lisha Sun, Yang Liu, Xudong Zhu, Xinbo Qiao, Qingtian Ma, Chao Liu, Nan Niu, Jinqi Xue, Guanglei Chen, Yongliang Yang, Caigang Liu
Summary: The KK-LC-1-FAT1-Hippo-ALDH1A1 pathway is identified as a therapeutic target in ALDH(+) cells of TNBC. The small-molecule inhibitor Z839878730 (Z8) can disrupt KK-LC-1 and FAT1 binding, reactivates the Hippo pathway, and suppresses TNBC tumor growth.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Yang Liu, Yueting Hu, Jinqi Xue, Jingying Li, Jiang Yi, Jiawen Bu, Zhenyong Zhang, Peng Qiu, Xi Gu
Summary: Immunotherapy has emerged as a promising strategy for treating triple-negative breast cancer (TNBC), which stimulates the immune system to kill tumor cells and offers new hope for patients. Breakthroughs in immune checkpoint inhibitors (ICIs) have led to individualized immunotherapy schedules and the combination with other treatment methods to overcome drug resistance.
Article
Biochemistry & Molecular Biology
Giovanni Pratelli, Daniela Carlisi, Diana Di Liberto, Antonietta Notaro, Michela Giuliano, Antonella D'Anneo, Marianna Lauricella, Sonia Emanuele, Giuseppe Calvaruso, Anna De Blasio
Summary: TNBC is an aggressive subtype of breast cancer characterized by resistance to anoikis, high invasiveness, and metastatic potential, as well as epithelial-mesenchymal transition (EMT) and stemness features. Inhibition of MCL1 using A-1210477 BH3-mimetic promotes anoikis/apoptosis, impairs focal adhesions, reduces migration and invasiveness, and downregulates EMT and stemness markers in MDA-MB-231 cell line.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Xiaoying Li, Yang Li, Xianqiang Du, Xu Wang, Shu Guan, Yu Cao, Feng Li, Feng Jin
Summary: The study indicates that HES1 promotes the stemness properties of BCSC in TNBC by upregulating Slug. TNBC patients with high levels of HES1 and Slug have worse prognosis. HES1 acts as a novel transcriptional activator for Slug, providing new insights for identifying promising prognostic biomarkers and therapeutic targets in TNBC.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Multidisciplinary Sciences
Jiahui Xu, Xiaoli Yang, Qiaodan Deng, Cong Yang, Dong Wang, Guojuan Jiang, Xiaohong Yao, Xueyan He, Jiajun Ding, Jiankun Qiang, Juchuanli Tu, Rui Zhang, Qun-Ying Lei, Zhi-min Shao, Xiuwu Bian, Ronggui Hu, Lixing Zhang, Suling Liu
Summary: Enhanced neovasculogenesis, especially vasculogenic mimicry (VM), contributes to the development of triple-negative breast cancer (TNBC). We identified TEM8 as a functional marker for VM-forming BTICs in TNBC, providing a target for the development of effective therapies against TNBC targeting both BTIC self-renewal and neovasculogenesis simultaneously. TEM8 promotes stemness and VM differentiation capacity through a RhoC/ROCK1/SMAD5 axis.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Wenwen Geng, Meiling Cao, Ke Dong, Junhua An, Haidong Gao
Summary: Our study revealed that aberrant activation of the mTOR pathway is a characteristic alteration in triple-negative breast cancer (TNBC), but the mTOR pathway inhibitor everolimus is not effective for TNBC patients. We identified that the activation of the ERK pathway is an important mechanism of resistance to everolimus in TNBC cells, and SHOC2 plays a critical role in mediating this pathway. Knockdown of SHOC2 significantly inhibited the activation of the Raf-ERK pathway induced by everolimus. Moreover, interference with SHOC2 expression in combination with everolimus had significant effects on cell cycle progression and apoptosis in vitro experiments.
CANCER BIOLOGY & THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Mokryun L. Baek, Junegoo Lee, Katherine E. Pendleton, Mariah J. Berner, Emily B. Goff, Lin Tan, Sara A. Martinez, Iqbal Mahmud, Tao Wang, Matthew D. Meyer, Bora Lim, James P. Barrish, Weston Porter, Philip L. Lorenzi, Gloria V. Echeverria
Summary: It was found that mitochondrial oxidative phosphorylation (OXPHOS) was elevated in triple negative breast cancer (TNBC) cells surviving neoadjuvant chemotherapy (NACT). DNA-damaging agents increased mitochondrial fusion and OXPHOS, while taxanes decreased these effects. Inhibiting mitochondrial fusion and fission suppressed regrowth of residual tumor cells. These findings offer potential strategies to overcome mitochondrial adaptations in chemoresistant TNBC.
Article
Cell Biology
Marie Winter, Samuel Meignan, Pamela Volkel, Pierre-Olivier Angrand, Valerie Chopin, Nadege Bidan, Robert-Alain Toillon, Eric Adriaenssens, Chann Lagadec, Xuefen Le Bourhis
Summary: The study reveals that TNBC cells become more invasive after chemotherapy, with vimentin potentially playing a role in enhancing tumor aggressiveness.
Article
Oncology
Min Xia, Xuyu Zu, Zuyao Chen, Gebo Wen, Jing Zhong
Summary: Triple-negative breast cancer (TNBC) is the most aggressive subtype among breast cancers, with high recurrence partly due to chemoresistance. Studies have shown that noncoding RNAs, especially miRNAs, lncRNAs, and circRNAs, play a role in TNBC resistance, suggesting that targeting ncRNAs may be a promising strategy to overcome chemoresistance.
Article
Pharmacology & Pharmacy
Cheng-Fang Tsai, Yu -Kai Cheng, Dah-Yuu Lu, Shu-Lin Wang, Chen-Ni Chang, Pei-Chun Chang, Wei-Lan Yeh
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2018)
Article
Food Science & Technology
Cheng-Fang Tsai, Jia-Hong Chen, Chen-Ni Chang, Dah-Yuu Lu, Pei-Chun Chang, Shu-Lin Wang, Wei-Lan Yeh
FOOD AND CHEMICAL TOXICOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Wen-Shin Chang, Te-Chun Shen, Wei-Lan Yeh, Chien-Chih Yu, Hui-Yi Lin, Hsi-Chin Wu, Chia-Wen Tsai, Da-Tian Bau
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Plant Sciences
Ya-Zhen Li, Jia-Hong Chen, Cheng-Fang Tsai, Wei-Lan Yeh
JOURNAL OF NATURAL PRODUCTS
(2019)
Article
Pharmacology & Pharmacy
Cheng-Fang Tsai, Jia-Hong Chen, Wei-Lan Yeh
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2019)
Article
Nutrition & Dietetics
Cheng-Fang Tsai, Guan-Wei Chen, Yen-Chang Chen, Ching-Kai Shen, Dah-Yuu Lu, Liang-Yo Yang, Jia-Hong Chen, Wei-Lan Yeh
Summary: Macrophage polarization plays essential roles in various diseases, and the natural compound quercetin has been found to inhibit inflammation and enhance M2 macrophage polarization and antioxidant expression. These findings are important for the potential use of quercetin as a drug for the treatment of inflammatory disorders in the central nervous system.
Article
Oncology
Yen-Chang Chen, Chen-Teng Wu, Jia-Hong Chen, Cheng-Fang Tsai, Chen-Yun Wu, Pei-Chun Chang, Wei-Lan Yeh
Summary: Diltiazem regulates EMT and cell motility in breast cancer cells by increasing GDF-15 expression.
Article
Nutrition & Dietetics
Wei-Lan Yeh, Bor-Ren Huang, Guan-Wei Chen, Vichuda Charoensaensuk, Cheng-Fang Tsai, Liang-Yo Yang, Dah-Yuu Lu, Mao-Kai Chen, Chingju Lin
Summary: Zerumbone effectively reduces the expression of lipocalin-2 and inhibits reactive oxygen species production in macrophages and microglial cells. In addition, it decreases the production of M1-polarization-associated chemokines and cytokines, while promoting the production of endogenous antioxidants and M2 macrophage polarization. The AMPK/Akt and Akt/GSK3 signaling pathways are involved in these effects.
Article
Biochemistry & Molecular Biology
Ching-Kai Shen, Bor-Ren Huang, Vichuda Charoensaensuk, Liang-Yo Yang, Cheng-Fang Tsai, Yu-Shu Liu, Dah-Yuu Lu, Wei-Lan Yeh, Chingju Lin
Summary: This study suggests that overexpression of B1R in GBM promotes TAM activity and modulates GBM progression, indicating that B1R could be an effective target for therapeutic methods in GBM.
Article
Oncology
Cheng-Fang Tsai, Jia-Hong Chen, Chen-Teng Wu, Pei-Chun Chang, Shu-Lin Wang, Wei-Lan Yeh
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY
(2019)