Article
Medicine, Research & Experimental
Xinjian Huang, Dongni Shi, Xuxiazi Zou, Xuxia Wu, Shumei Huang, Lingzhi Kong, Muwen Yang, Yunyun Xiao, Boyu Chen, Xiangfu Chen, Ying Ouyang, Libing Song, Yunting Jian, Chuyong Lin
Summary: This study found that BAG2 is significantly upregulated in relapse breast cancer patient tissues, and its high expression is associated with a worse prognosis. BAG2 localizes in mutant p53 aggregates and interacts with misfolded p53 mutants. BAG2 exacerbates the formation of the aggregates and recruits HSP90 to promote their propagation and maintenance, leading to chemoresistance in breast cancer.
Article
Cell Biology
Vinaya Phatak, Yannick von Grabowiecki, Justyna Janus, Leah Officer, Caron Behan, Lydia Aschauer, Lucia Pinon, Hannah Mackay, Sara Zanivan, Jim C. Norman, Michael Kelly, John Le Quesne, Patricia A. J. Muller
Summary: Mutant p53 protein can facilitate the cell membrane recycling of P-gp through RCP, leading to chemoresistance. Cells without RCP or mutant p53 show increased sensitivity to cisplatin and etoposide.
CELL DEATH & DISEASE
(2021)
Article
Oncology
Shuwei Chen, Muwen Yang, Chunyang Wang, Ying Ouyang, Xiangfu Chen, Jiewen Bai, Yameng Hu, Ming Song, Siyi Zhang, Quan Zhang
Summary: The study revealed that FOXD1 is upregulated in oral squamous cell cancer (OSCC) and promotes chemoresistance and epithelial-mesenchymal transition (EMT), with the CYTOR/LPP axis playing a key role in this process. FOXD1 may serve as a potential prognostic marker and therapeutic target for overcoming chemotherapy resistance in OSCC.
Article
Oncology
Yao Zhao, Chenchen Cai, Miaomiao Zhang, Lubing Shi, Jiwei Wang, Haoliang Zhang, Ping Ma, Shibao Li
Summary: The study revealed that Ephrin-A2 promotes prostate cancer metastasis by enhancing angiogenesis and promoting EMT, suggesting it may be a potential therapeutic target in metastatic prostate cancer.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Zhourui Ma, Shizhong Cai, Qianwei Xiong, Wei Liu, Hongliang Xia, Zhenhong Zhu, Zhijian Huang, Xiangming Yan, Qian Wang
Summary: This study reveals the role of WNT signaling in the chemoresistance of glioblastoma multiforme (GBM) to temozolomide (TMZ). The loss of function of p53 in GBM downregulates miR-34a expression, leading to the activation of WNT signaling and the resistance to TMZ. By targeting the miR-34a/WNT6 axis, drug sensitivity of p53-mutant GBM cells can be restored and overall survival can be extended.
Article
Environmental Sciences
Ruixue Huang, Chenjun Bai, Xiaodan Liu, Yao Zhou, Sai Hu, Decheng Li, Jing Xiang, Jihua Chen, Pingkun Zhou
Summary: This study identified a feedback loop involving p53, RMRP, miR122, and the Notch pathway that promotes EMT progression in silica-induced lung fibrosis. The upregulation of p53 upon silica exposure activates RMRP, which in turn decreases miR122 levels and activates the Notch signaling pathway. These findings provide new insights into the complex network regulating lung fibrosis.
Review
Oncology
Lobsang Dolma, Patricia A. J. Muller
Summary: In normal cells, p53 regulates cell cycle progression. However, in cancer, mutations in the p53 gene can cause the protein to lose its normal function and instead promote tumor growth and resistance to chemotherapy. This review discusses new strategies to target mutant p53-bearing cancers and reinstate sensitivity to chemotherapy.
Article
Oncology
Jie Jiang, Li Gao, Yongting Lan, Yang Wang, Peiqing Zhao
Summary: Previous studies have shown that TIPE1 acts as a tumor suppressor gene in several tumor types, but in cervical cancer, it promotes proliferation by inhibiting p53 activity, suppressing cell apoptosis, and facilitating chemoresistance in a p53-dependent manner. This suggests that TIPE1 plays a crucial role in the transition from chemosensitivity to chemoresistance and could be a potential target for cervical cancer chemotherapy.
FRONTIERS IN ONCOLOGY
(2021)
Article
Dentistry, Oral Surgery & Medicine
Juan Du, Wenjing Su, Xiaoguang Li, Tingjian Zu, Jinbo Bai, Weidong Zhang, Wei Zhou
Summary: In this study, the function of the long non-coding RNA LINC00525 in the progression of oral squamous cell carcinoma (OSCC) was investigated through in vitro and in vivo experiments. The results showed that LINC00525 was associated with OSCC survival and prognosis. Knockdown of LINC00525 decreased cell viability, migration and invasion properties, and increased apoptosis in OSCC cells. In vivo experiments also demonstrated that downregulation of LINC00525 reduced OSCC tumour growth. Therefore, LINC00525 may serve as a potential target for the treatment of OSCC.
Article
Biochemistry & Molecular Biology
Julie Xia Zhou, Ewud Agborbesong, Linda Xiaoyan Li, Xiaogang Li
Summary: This study reveals a novel regulatory mechanism of mutant p53 through BRD4 in triple-negative breast cancer (TNBC). Inhibition of BRD4 reduces the transcription of mutant p53 and suppresses the tumorigenesis of TNBC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Lindsay N. Redman-Rivera, Timothy M. Shaver, Hailing Jin, Clayton B. Marshall, Johanna M. Schafer, Quanhu Sheng, Rachel A. Hongo, Kathryn E. Beckermann, Ferrin C. Wheeler, Brian D. Lehmann, Jennifer A. Pietenpol
Summary: The study reveals that mutant p53 proteins with gain-of-function activities lead to diverse oncogenic phenotypes, and aneuploidy may drive some of these characteristics.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Oleg Semenov, Alexandra Daks, Olga Fedorova, Oleg Shuvalov, Nickolai A. Barlev
Summary: The aberrantly activated EMT program plays a central role in defining the critical features of aggressive carcinomas, and the p53 gene is critical for suppressing these features. Specific mutations in the p53 gene can convert it into an oncogene. This review contrasts the different regulatory roles of wild-type and mutant p53 in the process of EMT.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Lubna Therachiyil, Roopesh Krishnankutty, Fareed Ahmad, Jericha M. Mateo, Shahab Uddin, Hesham M. Korashy
Summary: This study reveals that activation of aryl hydrocarbon receptor (AhR) affects the progression and metastasis of ovarian cancer, potentially mediated by the activation of the PI3K/Akt, Wnt/β-catenin, and EMT pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Luisa Klemke, Clara F. Fehlau, Nadine Winkler, Felicia Toboll, Shiv K. Singh, Ute M. Moll, Ramona Schulz-Heddergott
Summary: Research has found that different alleleic mutations of mutant p53 gene (mutp53) in pancreatic ductal adenocarcinoma (PDAC) have specific oncogenic functions, mainly promoting invasion and metastasis to drive tumor progression. Similar to colorectal cancer (CRC), specific alleles of mutp53 exert enhanced functions by binding to and hyperactivating STAT3. This discovery suggests potential therapeutic vulnerabilities in targeting GOF mutp53 proteins in PDAC.
FRONTIERS IN ONCOLOGY
(2021)
Article
Pharmacology & Pharmacy
Yuqin Di, Xiaoqian Jing, Kunhua Hu, Xiangqiong Wen, Lvlan Ye, Xiang Zhang, Jiale Qin, Jinning Ye, Run Lin, Ziyang Wang, Weiling He
Summary: In this study, it was revealed that Oxaliplatin chemoresistance in colorectal cancer (CRC) is a major challenge in clinical treatment. The overexpression of WDR43 was found to be associated with poor prognosis in CRC patients. WDR43 knockdown inhibited cell growth and enhanced the effect of oxaliplatin chemotherapy by arresting cell cycle. Mechanistically, c-MYC promoted the transcriptional regulation and expression of WDR43. WDR43 enhanced the ubiquitination of p53 by MDM2 through binding to RPL11, leading to reduced stability of p53 protein and inducing proliferation and chemoresistance in CRC cells.
DRUG RESISTANCE UPDATES
(2023)
Article
Oncology
Francesca Menghi, Floris P. Barthel, Vinod Yadav, Ming Tang, Bo Ji, Zhonghui Tang, Gregory W. Carter, Yijun Ruan, Ralph Scully, Roel G. W. Verhaak, Jos Jonkers, Edison T. Liu
Meeting Abstract
Oncology
Sk. Kayum Alam, Matteo Astone, Ping Liu, Stephanie R. Hall, Abbygail M. Coyle, Erin N. Dankert, Dane K. Hoffman, Wei Zhang, Rui Kuang, Anja C. Roden, Aaron S. Mansfield, Luke H. Hoeppner
Article
Biochemical Research Methods
Ting-You Wang, Li Wang, Sk Kayum Alam, Luke H. Hoeppner, Rendong Yang
Article
Genetics & Heredity
Arindam Datta, Pijush Das, Sanjib Dey, Sangeeta Ghuwalewala, Dishari Ghatak, Sk Kayum Alam, Raghunath Chatterjee, Susanta Roychoudhury
Article
Oncology
Sk. Kayum Alam, Li Wang, Yanan Ren, Christina E. Hernandez, Farhad Kosari, Anja C. Roden, Rendong Yang, Luke H. Hoeppner
BRITISH JOURNAL OF CANCER
(2020)
Article
Biochemistry & Molecular Biology
Ting-You Wang, Qi Liu, Yanan Ren, Sk Kayum Alam, Li Wang, Zhu Zhu, Luke H. Hoeppner, Scott M. Dehm, Qi Cao, Rendong Yang
Summary: Exitron splicing (EIS) functions in cancer by affecting 63% of human coding genes, 95% of which are tumor specific. EIS alters cancer driver genes, leading to gain- or loss-of-function, and also produces neoepitopes that bind to MHC class I or II. Analysis of clinical data shows a correlation between EIS-derived neoantigen load and checkpoint inhibitor response in clear cell renal cell carcinoma.
Article
Cell Biology
Li Wang, Matteo Astone, Sk Kayum Alam, Zhu Zhu, Wuhong Pei, David A. Frank, Shawn M. Burgess, Luke H. Hoeppner
Summary: Vascular permeability triggered by inflammation or ischemia promotes edema and worsens disease progression, while VEGF plays a crucial role in regulating vascular barrier function. Targeting STAT3 can effectively reduce vascular permeability induced by VEGF.
DISEASE MODELS & MECHANISMS
(2021)
Article
Medicine, General & Internal
Stella P. Hartono, Victoria M. Bedell, Sk Kayum Alam, Madelyn O'Gorman, MaKayla Serres, Stephanie R. Hall, Krishnendu Pal, Rachel A. Kudgus, Priyabrata Mukherjee, Davis M. Seelig, Alexander Meves, Debabrata Mukhopadhyay, Stephen C. Ekker, Luke H. Hoeppner
Summary: This study demonstrates that activation of the VEGF pathway is a direct consequence of acute UV exposure and plays a role in the development of sunburn. Targeting VEGF signaling can prevent the acute effects of sunburn, suggesting a potential therapeutic approach for reducing UV-induced skin damage.
MAYO CLINIC PROCEEDINGS
(2022)
Article
Biochemistry & Molecular Biology
Sk. Kayum Alam, Yongchang Zhang, Li Wang, Zhu Zhu, Christina E. Hernandez, Yuling Zhou, Nong Yang, Jian Lei, Xiaoyan Chen, Liang Zeng, Mark A. Klein, Luke H. Hoeppner
Summary: The study reveals that DARPP-32 and kinase-activated EGFR and ERBB3 proteins are overexpressed in EGFR TKI-refractory LUAD, leading to the evasion of cell death through a specific mechanism.
Article
Oncology
Sk. Kayum Alam, Li Wang, Zhu Zhu, Luke H. Hoeppner
Summary: Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases and is often diagnosed at advanced stages with therapy-refractory disease progression. Understanding the molecular mechanisms of NSCLC progression is crucial for developing new therapies. Overexpression of I kappa B kinase alpha (IKK alpha) in NSCLC is associated with poor patient survival. Our study reveals that IKK alpha phosphorylates DARPP-32, inhibiting protein phosphatase 1 (PP1) and activating ERK signaling, promoting lung oncogenesis. Inhibition of IKK alpha reduces anchorage-independent growth in NSCLC cells and inhibits lung tumor growth in mice. These findings highlight the importance of IKK alpha in driving NSCLC growth through DARPP-32-mediated ERK activation.
NPJ PRECISION ONCOLOGY
(2023)
Meeting Abstract
Oncology
Sk Kayum Alam, Li Wang, Yanan Ren, Christina E. Hernandez, Farhad Kosari, Anja C. Roden, Rendong Yang, Luke H. Hoeppner
Article
Psychiatry
Aparna Ashok, Safoora Naaz, Lakshmi Narayanan Kota, Somdatta Sen, Meera Purushottam, Mohammed Faruq, Renu Kumari, Vinod Yadav, Ramakrishnan Kannan, Sanjeev Jain, Mitradas M. Panicker, Biju Viswanath
ASIAN JOURNAL OF PSYCHIATRY
(2019)
Article
Biology
Sk Kayum Alam, Matteo Astone, Ping Liu, Stephanie R. Hall, Abbygail M. Coyle, Erin N. Dankert, Dane K. Hoffman, Wei Zhang, Rui Kuang, Anja C. Roden, Aaron S. Mansfield, Luke H. Hoeppner
COMMUNICATIONS BIOLOGY
(2018)
Meeting Abstract
Oncology
Edison T. Liu, Francesca Menghi, Floris Barthel, Vinod Yadav, Ming Tang, Bo Ji, Gregory Carter, Jos Jonkers, Roeland Verhaak
Review
Oncology
Matteo Astone, Erin N. Dankert, Sk. Kayum Alam, Luke H. Hoeppner
NPJ PRECISION ONCOLOGY
(2017)