Article
Immunology
Abrar Ul Haq Khan, Alaa Kassim Ali, Bryan Marr, Donghyeon Jo, Simin Ahmadvand, Claire Fong-McMaster, Saeedah Musaed Almutairi, Lisheng Wang, Subash Sad, Mary-Ellen Harper, Seung-Hwan Lee
Summary: Natural killer (NK) cells upregulate the expression of TNF receptor 2 (TNFR2) and CD25 in response to infection/inflammation, which enhances their proliferation, metabolic activity, and effector function. The TNFa-TNFR2 signaling pathway leads to a metabolic switch towards aerobic glycolysis and is crucial for NK cell function.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Article
Oncology
Weikun Qian, Ke Chen, Tao Qin, Ying Xiao, Jie Li, Yangyang Yue, Cancan Zhou, Jiguang Ma, Wanxing Duan, Jianjun Lei, Liang Han, Li Li, Xin Shen, Zheng Wu, Qingyong Ma, Zheng Wang
Summary: In this study, pharmacological inhibition of HSF1 was found to slow pancreatic cancer initiation and suppress pancreatitis-induced formation of pancreatic precancerous lesions. Bioinformatics analysis revealed a close link between HSF1 and the EGFR pathway, with their parallel activation in pancreatic precancerous lesions. Additionally, inhibition of EGFR was shown to suppress pancreatic cancer initiation and HSF1 activation in vivo, indicating a partly HSF1-dependent mechanism of EGFR-mediated pancreatic cancer tumorigenesis.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Kento Okamoto, Toshinori Ando, Hiroki Izumi, Susumu S. Kobayashi, Tomoaki Shintani, J. Silvio Gutkind, Souichi Yanamoto, Mutsumi Miyauchi, Mikihito Kajiya
Summary: The Hippo signaling pathway and its downstream effector YAP play a central role in cell proliferation. Dysregulation of the Hippo pathway triggers YAP hyperactivation, thereby inducing head and neck squamous cell carcinoma (HNSCC). Our findings suggest that co-targeting both AXL and EGFR represent a promising therapeutic approach in patients with EGFR-altered cancers.
Article
Multidisciplinary Sciences
Ana Sousa-Ortega, Javier Vazquez-Marin, Estefania Sanabria-Reinoso, Jorge Corbacho, Rocio Polvillo, Alejandro Campoy-Lopez, Lorena Buono, Felix Loosli, Maria Almuedo-Castillo, Juan R. Martinez-Morales
Summary: YAP signaling is involved in regulating cell migration during embryonic axis assembly by sustaining intracellular tension. Knockout of yap and yap1b in medaka disrupts axis assembly and reduces cell displacement and migratory persistence. Yap targets genes involved in cytoskeletal organization and cell-ECM adhesion to promote cortical actin and focal adhesions recruitment in migratory cells.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Ji Won Kim, Cuyler Luck, Wei Wu, Rovingaile Kriska Ponce, Yone Kawe Lin, Nehal Gupta, Ross A. Okimoto
Summary: In this study, the researchers demonstrated a direct interaction between CIC and YAP1 in the MAPK-ERK pathway, and showed that inhibiting YAP1 could be a potential therapeutic strategy for CIC-deficient cancers.
Article
Oncology
Tianshi Wang, Dehai Wang, Yanan Sun, Ting Zhuang, Xin Li, Huijie Yang, Yifeng Zang, Ziping Liu, Penghe Yang, Chenmiao Zhang, Jiayao Cui, Mingxi Fu, Shuqing Zhang, Peng Su, Zhongbo Li, Jian Zhu, Yinlu Ding
Summary: We identified CXCR7 as an important modulator of the Hippo/YAP axis in gastric cancer progression, and demonstrated that CXCR7 activation can stimulate gastric cancer cell progression through this pathway. Additionally, we found that YAP can promote transcription of CXCR7, indicating that CXCR7 is an upstream signal of the Hippo/YAP axis.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Cell Biology
Tao Zhang, Ruiting Hu, Yan Wang, Shuai Guo, Zhimin Wu, Junfeng Liu, Chunyang Han, Changwei Qiu, Ganzhen Deng
Summary: The integrity of the endometrium is crucial for maintaining fertility, but the mechanisms for repairing uterine injuries are mostly unknown. This study reveals that disturbances in mechanical cues contribute to uterine injury. By identifying YAP as a sensor for biophysical forces, the researchers demonstrated that mechanical cues related to extracellular matrix rigidity can activate YAP and promote uterine remodeling. These findings shed new light on the regulatory mechanisms behind uterine remodeling and mechanotransduction.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Oncology
Hee Sun Park, Da-Hye Lee, Da Hyun Kang, Min-Kyung Yeo, Goeun Bae, Dahye Lee, Geon Yoo, Ju-Ock Kim, Eunyoung Moon, Yang Hoon Huh, Sang-Hee Lee, Eun-Kyeong Jo, Sang Yeon Cho, Jeong Eun Lee, Chaeuk Chung
Summary: This study highlights the role of the autophagy adaptor p62 in EGFR-TKI-resistant lung adenocarcinoma, demonstrating its oncogenic functions in promoting cell proliferation and invasion. The research also reveals the regulation of p62 transcription by YAP through ERK, with potential implications for targeting the YAP-p62 signaling axis in suppressing EGFR-TKI-resistant lung cancer. Targeting the YAP-p62 axis with the drug repurposing of verteporfin may provide a valuable approach for lung cancer treatment by inhibiting critical oncogenic targets simultaneously.
Article
Oncology
Dian-Qi Li, Ci-Cheng Huang, Guang Zhang, Lei-Lei Zhou
Summary: Translation: N6-methyladenosine (m6A) is a reversible modification of mRNA, and fat mass and obesity-associated (FTO) is an enzyme that can erase this modification. This study investigated the role of FTO in oral squamous cell carcinoma (OSCC). High levels of FTO were found in OSCC cell lines and tissues, and patients with high FTO had worse prognosis. Knockdown of FTO inhibited OSCC cell viability and tumor growth. FTO depletion increased YAP1 mRNA modification, leading to its degradation. Nucleocytoplasmic shuttling of FTO was critical for this process. Targeting the FTO/YAP1 axis may be a promising intervention for OSCC.
Article
Multidisciplinary Sciences
Xiaojing Yang, Jina Nanayakkara, Duncan Claypool, Sadegh Saghafinia, Justin J. M. Wong, Minqi Xu, Xiantao Wang, Christopher J. B. Nicol, Iacovos P. Michael, Markus Hafner, Xiaolong Yang, Neil Renwick
Summary: The miR-375/YAP axis plays a critical role in neuroendocrine differentiation and tumorigenesis in lung carcinoid cells, affecting functions such as neural differentiation, exocytosis, and secretion. This axis involves distinct transcriptomic changes, leading to significant reductions in cell proliferation, transformation, and tumor growth.
SCIENTIFIC REPORTS
(2021)
Article
Gastroenterology & Hepatology
Li Gu, Yahui Zhu, Xi Lin, Bingjun Lu, Xinyi Zhou, Feng Zhou, Qiu Zhao, Edward Prochownik, Youjun Li
Summary: This study identified an essential and wide-spread role of the IKK β-USP30-ACLY axis in tumor metabolism, which may be a potential therapeutic target in HCC.
Article
Biology
Toshinori Ando, Nadia Arang, Zhiyong Wang, Daniela Elena Costea, Xiaodong Feng, Yusuke Goto, Hiroki Izumi, Mara Gilardi, Kazuyo Ando, J. Silvio Gutkind
Summary: The Hippo pathway is frequently dysregulated in cancer, leading to unrestrained activity of its downstream targets, YAP/TAZ, and aberrant tumor growth. EGFR activates YAP/TAZ in HNSCC independently of its typical signaling targets, leading to potential drug resistance mechanisms in cancers with activated EGFR. Inhibition of YAP/TAZ in combination with EGFR might be beneficial to prevent treatment resistance and cancer recurrence.
COMMUNICATIONS BIOLOGY
(2021)
Article
Oncology
Minling Gao, Yi Fu, Weiqiang Zhou, Gege Gui, Bachuchu Lal, Yunqing Li, Shuli Xia, Hongkai Ji, Charles G. Eberhart, John Laterra, Mingyao Ying
Summary: This study focuses on uncovering the key signaling pathways of EGFR/TAF, and identifies osimertinib as an effective inhibitor that can treat cancers like GBM effectively.
Article
Multidisciplinary Sciences
Liwen Fu, Yanlin Liu, Guochen Qin, Ping Wu, Hailing Zi, Zhongtian Xu, Xiaodi Zhao, Yue Wang, Yaxing Li, Shuhui Yang, Chao Peng, Catherine C. L. Wong, Sang-Dong Yoo, Zecheng Zuo, Renyi Liu, Young-Hee Cho, Yan Xiong
Summary: The evolutionarily conserved TOR kinase acts as a master regulator coordinating cell proliferation and growth among eukaryotes. Research has shown that TOR directly phosphorylates EIN2 to regulate a wide range of genes involved in various metabolic pathways. This study reveals a molecular mechanism by which different signaling pathways can modulate a central signaling hub through distinct phosphorylation codes.
Article
Cell Biology
Binbin Chen, Huimou Chen, Suying Lu, Xiaoqin Zhu, Yi Que, Yu Zhang, Junting Huang, Li Zhang, Yu Zhang, Feifei Sun, Juan Wang, Jia Zhu, Zijun Zhen, Yizhuo Zhang
Summary: Upregulated histone demethylase KDM5B in Ewing sarcoma (EwS) was found to be associated with poor prognosis. KDM5B is involved in regulating the cell cycle pathway and affects the accumulation of CCNE1 protein. Targeting KDM5B with epigenetic drugs could be a potential treatment for EwS.
CELL DEATH & DISEASE
(2022)