Article
Biochemistry & Molecular Biology
Sixian Qi, Zhenxing Zhong, Yuwen Zhu, Yebin Wang, Mingyue Ma, Yu Wang, Xincheng Liu, Ruxin Jin, Zhihan Jiao, Rui Zhu, Zhao Sha, Kyvan Dang, Ying Liu, Dae-Sik Lim, Junhao Mao, Lei Zhang, Fa-Xing Yu
Summary: This study reveals that the HPO1 and HPO2 modules together regulate the activity of LATS1/2 kinases and YAP/TAZ transcriptional co-activators in the Hippo pathway. Inactivation of either HPO1 or HPO2 module leads to partial activation of YAP/TAZ, bile duct hyperplasia, and hepatocellular carcinoma (HCC) in mice livers. On the other hand, inactivation of both HPO1 and HPO2 modules results in full activation of YAP/TAZ, rapid development of intrahepatic cholangiocarcinoma (iCCA), and early lethality.
Article
Cell Biology
Monserrat Gerardo-Ramirez, Vanessa Giam, Diana Becker, Marco Groth, Nils Hartmann, Helen Morrison, Helen L. May-Simera, Markus P. Radsak, Jens U. Marquardt, Peter R. Galle, Peter Herrlich, Beate K. Straub, Monika Hartmann
Summary: Primary liver cancer is a major cause of cancer-related death globally. The Hippo tumor suppressor pathway and its upstream regulator Merlin have been found to play critical roles in cell proliferation and fate determination in the liver. This study evaluated the contribution of CD44 and Merlin-dependent processes to liver tumor development and progression. While Merlin deletion led to liver enlargement and the formation of various liver tumors, deletion of CD44 had no effect on primary liver tumor development but significantly inhibited metastasis formation. CD44 upregulates integrin beta 2 expression and promotes transendothelial migration of liver cancer cells, suggesting it as a potential target for intervention in liver cancer metastasis.
Article
Biochemistry & Molecular Biology
Qifeng Sun, Hongda Lu, Wenjie Zhang, Yang Du, Qian Liang, Yehui Zhang, Jing Wu, Mingwei Zhong
Summary: This study reveals the oncogenic role of RNF106, a modifier of DNA methylation and histone ubiquitination, in esophageal squamous cell carcinoma (ESCC). It is found that RNF106 is involved in ESCC cell migration and invasion, and its expression is associated with poor survival in ESCC patients. Mechanistic studies demonstrate that RNF106 promotes YAP oncogenic function by regulating LATS2 ubiquitination and degradation in ESCC.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Editorial Material
Cell Biology
Solmaz Sahebjam, Mark R. Gilbert
Summary: Loss of NF2 gene and YAP1-MAML2 fusion in meningiomas promote tumor formation through TEAD-dependent YAP1 activity. Pharmacological inhibition of YAP1-TEAD has shown antitumor activity in both YAP1 fusion-positive and NF2 mutant meningiomas. Disruption of the YAP1-TEAD interaction may provide a potential therapeutic option for these tumors.
GENES & DEVELOPMENT
(2022)
Article
Cell Biology
Frank Szulzewsky, Sonali Arora, Aleena K. S. Arakaki, Philipp Sievers, Damian A. Almiron Bonnin, Patrick J. Paddison, Felix Sahm, Patrick J. Cimino, Taranjit S. Gujral, Eric C. Holland
Summary: The study investigates the role of YAP1-MAML2 gene fusion in the formation of meningioma and demonstrates that YAP1-MAML2 is a causal oncogenic driver in meningioma.
GENES & DEVELOPMENT
(2022)
Article
Pharmacology & Pharmacy
Derek B. Oien, Sayantani Sarkar Bhattacharya, Jeremy Chien, Julian Molina, Viji Shridhar
Summary: The study showed that the combination of quinacrine and cisplatin could synergistically eliminate mesothelioma cells, and cells with NF2 mutations were highly sensitive to quinacrine. Quinacrine alters the expression of over 3000 genes in NF2-mutated cells and induces a G1 phase cell cycle arrest, suggesting its potential repurposing for a large subset of mesothelioma patients.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Gastroenterology & Hepatology
Jingsheng Ma, Yajun Wu, Shibao Cheng, Wentao Yang, Lin Zhong, Qigen Li, Lu Fang
Summary: This study investigates the role of FBXO22 in promoting pancreatic cancer growth. The researchers found that FBXO22 is upregulated in pancreatic cancer tissues and is associated with poor prognosis. Knockdown of FBXO22 inhibits pancreatic cancer cell growth, while overexpression accelerates it. Mechanistically, FBXO22 deactivates the Hippo pathway by directly interacting with and destabilizing LATS2. These findings shed light on the regulation of the Hippo pathway in pancreatic cancer growth and identify FBXO22 as a potential therapeutic target.
DIGESTIVE DISEASES AND SCIENCES
(2023)
Article
Oncology
Haitang Yang, Sean R. R. Hall, Beibei Sun, Liang Zhao, Yanyun Gao, Ralph A. Schmid, Swee T. Tan, Ren-Wang Peng, Feng Yao
Summary: The study revealed that loss-of-function in the upstream regulator NF2 of the Hippo pathway is associated with aberrant activation of Hippo-YAP-independent signaling, defining distinct MPM subsets with different molecular features and prognosis. This has important clinical implications for precision oncology in MPM patients.
Review
Cell Biology
Yong Suk Cho, Jin Jiang
Summary: The Hippo signaling pathway is an evolutionarily conserved tumor suppressor pathway that controls tissue growth and organ size by regulating cell proliferation and death, and is implicated in a wide range of human cancers. It consists of a kinase cascade regulated by various upstream signals.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Editorial Material
Oncology
Sean Dulloo, Aleksandra Bzura, Dean Anthony Fennell
Summary: Malignant pleural mesotheliomas (MPMs) exhibit a wide variation in natural history and genomic heterogeneity among patients and within tumors. Recent advancements in identifying genetic drivers and developing strategies to target vulnerabilities resulting from inactivation of key tumor suppressors suggest potential for novel molecular therapy approaches for mesothelioma.
Article
Oncology
Fengen Liu, Binhui Xie, Rong Ye, Yuankang Xie, Baiyin Zhong, Jinrong Zhu, Yao Tang, Zelong Lin, Huiru Tang, Ziqing Wu, Heping Li
Summary: In this study, it was found that overexpression of TRIM47 is associated with tumor progression and poor prognosis in triple-negative breast cancer. The researchers demonstrated that TRIM47 directly interacts with BRCA1 and induces proteasome turnover of BRCA1, leading to a decrease in BRCA1 protein levels in TNBC. Additionally, TRIM47 overexpression confers sensitivity to the PARP inhibitor olaparib, while TRIM47 inhibition confers resistance to olaparib in TNBC. Overexpression of BRCA1 also increases resistance to olaparib in TRIM47-overexpression-induced PARP inhibition sensitivity. These findings suggest that targeting the TRIM47/BRCA1 axis may be a promising prognostic factor and therapeutic target for TNBC.
Article
Biochemistry & Molecular Biology
Fei Liu, Qianying Han, Ting Zhang, Fen Chang, Jingcheng Deng, Xiaotian Huang, Weiping Wang, Yongjie Xu, Qin Li, Luzheng Xu, Bo Zhang, Wentong Li, Li Li, Yanrong Su, Yang Li, Genze Shao
Summary: In this study, researchers identified DCAF8L1 as an important E3 ligase that regulates the stability of BRCA1 and BARD1 tumor suppressor, linking BRCA1 and X chromosome inactivation to breast carcinogenesis.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Cell Biology
Zhenzhou Fang, Xingming Li, Yuki Yoshino, Moe Suzuki, Huicheng Qi, Hinari Murooka, Riko Katakai, Matsuyuki Shirota, Thi Anh Mai Pham, Ayako Matsuzawa, Kei Otsuka, Chikashi Ishioka, Takahiro Mori, Natsuko Chiba
Summary: This study reveals the role of Aurora A kinase in reducing centrosomal OLA1. Aurora A binds to and polyubiquitinates OLA1, while its kinase activity suppresses OLA1 polyubiquitination. The decreased centrosomal OLA1 caused by Aurora A-mediated polyubiquitination promotes the recruitment of pericentriolar material proteins in G2 phase.
Article
Cell Biology
Xi Liu, Feng Jiang, Zhilinag Wang, Lang Tang, Bin Zou, Pengfei Xu, Tenghua Yu
Summary: The study demonstrated that EVs derived from hypoxic bone marrow mesenchymal cells can deliver miR-328-3p to lung cancer cells, promoting cancer cell proliferation, invasion, and migration by targeting the NF2 gene to inhibit the Hippo pathway. This ultimately leads to the occurrence and progression of lung cancer.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Cell Biology
Zhengliang Li, Xiaojing Liu, Haizhou Yu, Shaoping Wang, Shuliang Zhao, Guoxiang Jiang
Summary: USP21 contributes to radio-resistance in cervical cancer cells through the FOXM1/Hippo signaling pathway, suggesting its potential as a target for radiosensitizers in radiotherapy.
Article
Geriatrics & Gerontology
Gerald S. Shadel, Peter D. Adams, W. Travis Berggren, Jolene K. Diedrich, Kenneth E. Diffenderfer, Fred H. Gage, Nasun Hah, Malene Hansen, Martin W. Hetzer, Anthony J. A. Molina, Uri Manor, Kurt Marek, David D. O'Keefe, Antonio F. M. Pinto, Alessandra Sacco, Tatyana O. Sharpee, Maxim N. Shokriev, Stefania Zambetti
Summary: Understanding the complexity and heterogeneity of the aging process is crucial for developing interventions to prevent age-related declines and diseases. Factors like genetics, environment, and the intrinsic heterogeneity of organs, tissues, and cell types all contribute to variable rates and trajectories of aging. To tackle this heterogeneity, new tools and computational approaches are needed to identify novel aging signatures and integrate disparate datasets, while improving human cell-based models for relevant research findings in aging and healthspan interventions.
Article
Oncology
Le Yu, Dan Zhou, Guiming Zhang, Zhonglu Ren, Xin Luo, Peng Liu, Steven W. Plouffe, Zhipeng Meng, Toshiro Moroishi, Yilei Li, Yiyue Zhang, Joan Heller Brown, Shuwen Liu, Kun-Liang Guan
Summary: The combined BAP1 deficiency and SF3B1 hotspot mutation in uveal melanoma lead to cell senescence, growth arrest, increased sensitivity to chemotherapeutic drugs, decreased DNA damage response, and reduced invasion capabilities. The co-occurrence of these mutations explains their mutual exclusivity in human UM.
MOLECULAR ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Hiroyuki Shinchi, Fumikazu Komaki, Masaharu Yuki, Haruka Ohara, Naohiro Hayakawa, Masahiro Wakao, Howard B. Cottam, Tomoko Hayashi, Dennis A. Carson, Toshiro Moroishi, Yasuo Suda
Summary: Synthetic small-molecule Toll-like receptor 7 (TLR7) ligands can serve as potential immunotherapeutic agents, and their formulation with macromolecules enhances their pharmaceutical properties. This study developed a second-generation glyco-nanoadjuvant and found that the linker length significantly affects the adjuvant activity.
ACS CHEMICAL BIOLOGY
(2022)
Article
Oncology
Daichi Nomoto, Yoshifumi Baba, Yang Liu, Hiroyasu Tsutsuki, Kazuo Okadome, Kazuto Harada, Takatsugu Ishimoto, Masaaki Iwatsuki, Shiro Iwagami, Yuji Miyamoto, Naoya Yoshida, Masayuki Watanabe, Toshiro Moroishi, Yoshihiro Komohara, Tomohiro Sawa, Hideo Baba
Summary: Fusobacterium nucleatum influences the progression of gastrointestinal cancers by invading and occupying cancer cells, impacting gene and protein expression, and activating signaling pathways. This study provides insights into the mechanism of ESCC progression induced by F. nucleatum.
Article
Cell Biology
Kristina Seiler, Magali Humbert, Petra Minder, Iris Mashimo, Anna M. Schlafli, Deborah Krauer, Elena A. Federzoni, Bich Vu, James J. Moresco, John R. Yates, Martin C. Sadowski, Ramin Radpour, Thomas Kaufmann, Jean-Emmanuel Sarry, Joern Dengjel, Mario P. Tschan, Bruce E. Torbett
Summary: This study found that HK3 is dispensable for glycolytic activity in AML cells while promoting cell survival, possibly through direct interaction with the BH3-only protein BIM during ATRA-induced neutrophil differentiation.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Luke Bu, Atsuko Yonemura, Noriko Yasuda-Yoshihara, Tomoyuki Uchihara, Galym Ismagulov, Sanae Takasugi, Tadahito Yasuda, Yuya Okamoto, Fumimasa Kitamura, Takahiko Akiyama, Kota Arima, Rumi Itoyama, Jun Zhang, Lingfeng Fu, Xichen Hu, Feng Wei, Yuichiro Arima, Toshiro Moroishi, Koichi Nishiyama, Guojun Sheng, Toshifumi Mukunoki, Jun Otani, Hideo Baba, Takatsugu Ishimoto
Summary: This study found that downregulation of 15-PGDH in the tumor microenvironment enhances the accumulation of PGE2 and promotes angiogenesis and CAF expansion in fibrotic tumors.
Article
Biochemistry & Molecular Biology
Haruki Horiguchi, Tsuyoshi Kadomatsu, Shinsei Yumoto, Takeshi Masuda, Keishi Miyata, Shuji Yamamura, Michio Sato, Jun Morinaga, Sumio Ohtsuki, Hideo Baba, Toshiro Moroishi, Yuichi Oike
Summary: Tumor cell-derived ANGPTL2 promotes beta-catenin-driven intestinal tumorigenesis by upregulating OB-cadherin expression and blocking destruction complex-independent proteasomal degradation of beta-catenin proteins. It also leads to decreased cell surface integrin alpha 5 beta 1 expression.
Article
Multidisciplinary Sciences
Baolei Yuan, Xuan Zhou, Keiichiro Suzuki, Gerardo Ramos-Mandujano, Mengge Wang, Muhammad Tehseen, Lorena Cortes-Medina, James J. Moresco, Sarah Dunn, Reyna Hernandez-Benitez, Tomoaki Hishida, Na Young Kim, Manal M. Andijani, Chongwei Bi, Manching Ku, Yuta Takahashi, Jinna Xu, Jinsong Qiu, Ling Huang, Christopher Benner, Emi Aizawa, Jing Qu, Guang-Hui Liu, Zhongwei Li, Fei Yi, Yanal Ghosheh, Changwei Shao, Maxim Shokhirev, Patrizia Comoli, Francesco Frassoni, John R. Yates, Xiang-Dong Fu, Concepcion Rodriguez Esteban, Samir Hamdan, Mo Li, Juan Carlos Izpisua Belmonte
Summary: In this study, the authors revealed that WASP deficiency results in aberrant RNA splicing and that WASP regulates the transcription of splicing factor genes and co-transcriptional RNA splicing through a phase-separation process involving splicing factors and nascent RNA.
NATURE COMMUNICATIONS
(2022)
Correction
Multidisciplinary Sciences
Baolei Yuan, Xuan Zhou, Keiichiro Suzuki, Gerardo Ramos-Mandujano, Mengge Wang, Muhammad Tehseen, Lorena V. Cortes-Medina, James J. Moresco, Sarah Dunn, Reyna Hernandez-Benitez, Tomoaki Hishida, Na Young Kim, Manal M. Andijani, Chongwei Bi, Manching Ku, Yuta Takahashi, Jinna Xu, Jinsong Qiu, Ling Huang, Christopher Benner, Emi Aizawa, Jing Qu, Guang-Hui Liu, Zhongwei Li, Fei Yi, Yanal Ghosheh, Changwei Shao, Maxim Shokhirev, Patrizia Comoli, Francesco Frassoni, John R. Yates, Xiang-Dong Fu, Concepcion Rodriguez Esteban, Samir Hamdan, Juan Carlos Izpisua Belmonte, Mo Li
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Taishi Yamane, Yohei Kanamori, Hiroshi Sawayama, Hiromu Yano, Akihiro Nita, Yudai Ohta, Hironori Hinokuma, Ayato Maeda, Akiko Iwai, Takashi Matsumoto, Mayuko Shimoda, Mayumi Niimura, Shingo Usuki, Noriko Yasuda-Yoshihara, Masato Niwa, Yoshifumi Baba, Takatsugu Ishimoto, Yoshihiro Komohara, Tomohiro Sawa, Tasuku Hirayama, Hideo Baba, Toshiro Moroishi
Summary: Accumulating evidence suggests that high levels of Fusobacterium nucleatum in colorectal tumor tissues can be associated with poor prognosis in patients with colorectal cancer (CRC). This study shows that high-iron status and F. nucleatum-positive are both associated with worse prognosis. Iron plays a key role in modulating the NF-KB signaling pathway.
Article
Biochemistry & Molecular Biology
Sujin Lee, Stephen Abini-Agbomson, Daniela S. Perry, Allen Goodman, Beiduo Rao, Manning Y. Huang, Jolene K. Diedrich, James J. Moresco, John R. R. Yates III, Karim-Jean Armache, Hiten D. Madhani
Summary: The Polycomb-like protein Ccc1 in Cryptococcus neoformans maintains the separation of HP1 and Polycomb heterochromatin domains through phase separation. The ability of Ccc1 to form condensates in vivo, which are enriched for PRC2, is dependent on its phase separation behavior driven by the intrinsically disordered region and the coiled-coil dimerization domain. Mutations that alter phase separation of Ccc1 lead to ectopic H3K27me3 at HP1 domains. These findings provide a biochemical basis for chromatin regulation where mesoscale biophysical properties play a crucial functional role.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Biochemical Research Methods
Antonio F. M. Pinto, Jolene K. Diedrich, James J. Moresco, John R. Yates III
Summary: Differential precipitation of proteins (DiffPOP) is a simple technique for fractionating complex protein mixtures. It enables the selective precipitation of ten distinct subsets of proteins, which can be identified using mass spectrometry-based proteomics. Addition of DiffPOP to a standard LC-MS proteomics workflow allows for a three-dimensional separation of peptides, resulting in increased protein coverage and peptide identifications. Importantly, DiffPOP reveals solubility differences between proteoforms, providing valuable insights that are often missed in bottom-up proteomics.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)
Article
Medicine, Research & Experimental
Manabu Kawata, Daniel B. McClatchy, Jolene K. Diedrich, Merissa Olmer, Kristen A. Johnson, John R. Yates, Martin K. Lotz
Summary: This study identified mocetinostat as a potential disease-modifying osteoarthritis drug (DMOAD) by upregulating the expression of Kruppel-like factor 4 (KLF4) and promoting regenerative and protective functions in joint tissues. The findings suggest that mocetinostat has therapeutic and protective activities against osteoarthritis, making it a candidate for further development as a DMOAD.
Article
Biochemical Research Methods
Casimir Bamberger, Sandra Pankow, Salvador Martinez-Bartolome, Jolene K. Diedrich, Robin S. K. Park, John R. Yates III
Summary: In this study, the researchers identified host proteins that interacted with the spike protein of SARS-CoV-2 using coimmunoprecipitation and mass spectrometry. They found that the spike protein bound to extracellular laminin and thrombospondin, as well as endoplasmic reticulum-resident DJB11 and FBX2 proteins. They also observed that the D614 spike protein had higher binding affinity to certain ER-resident proteins in the Alpha SARS-CoV-2 strain compared to the mutated G614 spike protein. This increased binding might enable SARS-CoV-2 to infect additional cell types that do not express ACE2.
JOURNAL OF PROTEOME RESEARCH
(2023)
Meeting Abstract
Oncology
Taishi Yamane, Hiroshi Sawayama, Takeshi Morinaga, Kosuke Mima, Masaaki Iwatsuki, Yoshifumi Baba, Takatsugu Ishimoto, Shiro Iwagami, Yuji Miyamoto, Naoya Yoshida, Toshiro Moroishi, Hideo Baba
