Article
Oncology
Lixin He, Huili Feng, Baoyi Yin, Wenxuan Li, Xiao Wang, Talha Umar, Hongbo Gao, Ning Zhou, Changwei Qiu
Summary: This study demonstrates that sodium new houttuyfonate (SNH) has a significant apoptotic effect on breast cancer by promoting the excessive accumulation of reactive oxygen species (ROS), inducing mitochondrial damage, regulating the aggregation of apoptotic proteins near mitochondria, and targeting the PDK1-AKT-GSK3 beta pathway. The results suggest that SNH may have significant therapeutic potential in breast cancer treatment.
Review
Oncology
Na Wang, Jianjiang Fu, Zhihua Li, Ningni Jiang, Yanhong Chen, Juan Peng
Summary: This review assesses the potential role of targeted PDK1 therapies in breast cancer (BC) and summarizes the current clinical trials. The study finds that although there is currently no selective PDK1 inhibitor available for BC therapy, combination trials of PDK1-targeted therapy and other agents have shown some benefit. This provides a new approach for the treatment of BC.
Article
Biochemistry & Molecular Biology
Ruiman Geng, Nengwen Ke, Ziyao Wang, Yu Mou, Bin Xiang, Zhengkun Zhang, Xuxu Ji, Jiaqiong Zou, Dingxue Wang, Zhaoru Yin, Xubao Liu, Fang Xie, Yanan Zhao, Dan Chen, Jingying Dong, Wenbing Wu, Lihong Chen, Huawei Cai, Ji Liu
Summary: Cuproplasia, or copper-dependent cell proliferation, has been observed in various solid tumors, and understanding the role of copper transporters in tumor biology could lead to new cancer treatment strategies. In this study, researchers investigated the significance of high-affinity copper transporter-1 (CTR1) in pancreatic cancer and found that hyperactive CTR1 promotes tumor growth and progression by activating the AKT/mTOR signaling pathway. Depletion of intracellular copper inhibited proliferation and angiogenesis of pancreatic cancer cells and improved the anti-cancer effect of an mTOR inhibitor. These findings suggest that targeting CTR1 and copper homeostasis may be a promising approach for cancer therapy.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Biochemistry & Molecular Biology
Xiang-Yu Guo, Tian-Tian Liu, Wen-Jie Zhu, Hai-Ting Liu, Guo-Hao Zhang, Lin Song, Rui-Nan Zhao, Xu Chen, Peng Gao
Summary: This study reveals the tumor-suppressor role of circKDM4B in breast cancer, especially in inhibiting tumor growth, metastasis, and angiogenesis, making it a potential therapeutic target for breast cancer progression.
Article
Cell Biology
Changle Ji, Linbo Zhu, Lin Fang
Summary: This study identified a novel circRNA, hsa_circ_0000851, which is involved in the pathogenesis of breast cancer. The study found that hsa_circ_0000851 was upregulated in breast cancer cells and promoted cell proliferation and migration through the miR-1183/PDK1/p-AKT pathway.
CELLULAR SIGNALLING
(2023)
Article
Multidisciplinary Sciences
Yue Qi, Qingqing Yao, Xuanyan Li, Xinyu Li, Wenwen Zhang, Pengpeng Qu
Summary: This study investigates the role of SLC31A1, an important copper transporter, in human malignancies and its association with cancer prognosis. The findings show that SLC31A1 expression is elevated in cervical, endometrial, and breast cancers, but reduced in clear cell renal cell carcinoma, liver hepatocellular carcinoma, and lung adenocarcinoma. SLC31A1 expression is strongly correlated with overall survival and disease-free survival in several cancers. Furthermore, SLC31A1 gene mutations and methylations were identified in 33 cancers. These results provide valuable insights into the role of SLC31A1 in pan-cancer profiles and suggest its potential as a predictive biomarker, particularly in gynaecological cancers.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Fang Huang, Jian Cui, Jingxuan Wan, Xue Yuan, Yuanzhe Zhu, Xiangxiang Wu, Wei Zuo, Tiantian Zhao
Summary: SLC12A8 mediates TKI resistance in EGFR-mutant lung cancer through the PDK1/AKT axis.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Nanoscience & Nanotechnology
Guangqi Song, Haisi Dong, Danhui Ma, Heming Wang, Xinran Ren, Yishen Qu, Hao Wu, Jimin Zhu, Wu Song, Ying Meng, Li Wang, Taotao Liu, Xizhong Shen, Yicheng Zhao, Changfeng Zhu
Summary: Copper is essential for various life processes but can be highly toxic at excessive levels. In multiple malignancies, including pancreatic cancer, copper overload is common, and targeting metal ion transporters for treatment may offer an effective strategy. Therapeutic tFNAs may serve as vehicles for delivering small molecular RNAs to regulate copper intake in cancer cells, potentially attenuating cancer progression.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Chemistry, Medicinal
Rangru Liu, Zhuo Chen, Gaoyun Hu, Zutao Yu, Qianbin Li, Danqi Liu, Ling Li, Zhaoqian Liu
Summary: In this study, a series of new PDK1/MEK dual inhibitors were synthesized, and Compound YZT showed strong inhibitory action in A549 cells. The mechanisms of YZT against non-small cell lung cancer (NSCLC) were investigated, and it was found that YZT has anti-proliferation and pro-apoptosis effects in NSCLC cells. YZT-induced autophagy was found to be cytoprotective and mediated by the PDK1/Akt/mTOR signaling axis.
Article
Cell Biology
Rui Liu, Lin Liu, Yan Bian, Shinan Zhang, Yue Wang, Huajian Chen, Xinyue Jiang, Guanghui Li, Qing Chen, Chang Xue, Mengke Li, Lianchang Liu, Xiaodong Liu, Shumei Ma
Summary: This study investigated whether ionizing radiation (IR) can induce ferroptosis in breast cancer and elucidated the molecular mechanisms involved. The results revealed that the ferroptosis-related gene SLC7A11 was highly expressed in breast cancer tissues and was associated with poor survival. Furthermore, the study demonstrated the coordinated function of ESR1 and NEDD4L in regulating SLC7A11 expression and inducing ferroptosis in breast cancer cells after radiation treatment.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Chemistry, Medicinal
Macus Tien Kuo, Yu-Fang Huang, Cheng-Yang Chou, Helen H. W. Chen
Summary: Platinum-containing antitumor drugs, such as cisplatin, carboplatin, and oxaliplatin, have been effective in treating various human malignancies by targeting DNA. Recent research emphasizes the significance of the copper transport system in cancer therapy. Modulating cellular copper levels can impact the transport and efficacy of platinum-based chemotherapy drugs.
Article
Multidisciplinary Sciences
Qiwei Jiang, Xiaomei Zhang, Xiaoming Dai, Shiyao Han, Xueji Wu, Lei Wang, Wenyi Wei, Ning Zhang, Wei Xie, Jianping Guo
Summary: The study demonstrates that S6K1 can directly phosphorylate PDK1, inhibiting the activity of AKT kinase and its role in tumorigenesis. This feedback regulation of AKT signaling through S6K1-mediated PDK1 phosphorylation provides insight into the regulation of the AKT pathway and potential strategies for combating mutant PDK1-driven cancers.
NATURE COMMUNICATIONS
(2022)
Article
Dentistry, Oral Surgery & Medicine
Lu-Ming Wang, Ye-Hua Gan
Summary: The study showed that knockdown of cancer-derived IgG (CIgG) enhanced the effects of cisplatin in oral squamous cell carcinoma through the PTP-BAS/Src/PDK1/AKT signaling pathway. The knockdown of CIgG promoted cisplatin-induced cell apoptosis and inhibition of cell proliferation, migration, and invasion. The study also found that cisplatin upregulated CIgG expression and phosphorylation of AKT and PDK1.
Article
Biochemistry & Molecular Biology
Dong Han, Wei Wang, Julie Heejin Jeon, Tao Shen, Xiangsheng Huang, Ping Yi, Bingning Dong, Feng Yang
Summary: Phosphoinositide-dependent kinase-1 (PDK1) is a master kinase that regulates cancer cell proliferation, survival, and metabolism. It phosphorylates/activates AKT and other AGC kinases, including MAPK4, promoting tumor growth. MAPK4 can independently promote AKT activation and tumor growth, and also enhance PDK1 protein synthesis, leading to the activation of PDK1 substrates beyond AKT. Co-targeting AKT and PDK1 effectively represses MAPK4-induced cancer cell growth, providing a potential therapeutic strategy for MAPK4-high cancers.
Article
Biochemistry & Molecular Biology
Lin Liu, Chen Zhang, Shugen Qu, Rui Liu, Huajian Chen, Zhenzhen Liang, Zhujun Tian, Lan Li, Shumei Ma, Xiaodong Liu
Summary: This study found that overexpression of ESR1 is associated with decreased overall survival in estrogen receptor-positive breast cancer. There is a regulatory relationship between ESR1 and NEDD4L/CD71, which plays an important role in IR-induced ferroptosis and may be a potential target for radiotherapy in breast cancer.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)