Article
Biochemistry & Molecular Biology
Jennifer J. McCann, Irina A. Vasilevskaya, Christopher McNair, Peter Gallagher, Neermala Poudel Neupane, Renee de Leeuw, Ayesha A. Shafi, Emanuela Dylgjeri, Amy C. Mandigo, Matthew J. Schiewer, Karen E. Knudsen
Summary: The tumor suppressor gene TP53 is frequently mutated in prostate cancer, with missense mutations at specific hotspots like R273. Mutant p53 variants R273C and R273H exhibit similar loss of DNA binding and transcriptional function in the absence of wild-type p53, but show distinct transcriptional profiles when wild-type p53 is present. Additionally, modeling of heterozygous expression of these mutants results in different phenotypic outcomes in vitro and in vivo, highlighting the context-dependent pro-tumorigenic role of mutant p53 in prostate cancer progression.
Article
Cell Biology
Yuhan Chang, Juan Zhang, Xinying Huo, Xinliang Qu, Chunlei Xia, Kaizong Huang, Fuyang Xie, Nuofan Wang, Xiaowei Wei, Qiong Jia
Summary: In this study, it is found that the F-actin regulator CRAD plays a negative role in the progression, stemness, and metastasis of colorectal cancer. Mechanistically, decreased CRAD in soft substrates enhances the stemness and metastasis potential of colorectal cancer by affecting the localization of YAP and the expression of stemness markers. Furthermore, CRAD deficiency also promotes colorectal tumor cell softening and epithelial-mesenchymal transition, contributing to its metastasis potential.
Article
Genetics & Heredity
Wei Zheng, Luisa Tasselli, Tie-mei Li, Katrin F. Chua
Summary: The modulation of dynamic histone acetylation states is crucial for gene expression and chromatin structure. SIRT6 controls nuclear levels of ACLY and regulates the expression of tumor suppressive genes by affecting nuclear acetyl-CoA pools.
Article
Oncology
Huijie Yang, Min Xue, Peng Su, Yan Zhou, Xin Li, Zhongbo Li, Yan Xia, Chenmiao Zhang, Mingxi Fu, Xiuxia Zheng, Guosheng Luo, Tian Wei, Xinxing Wang, Yinlu Ding, Jian Zhu, Ting Zhuang
Summary: In this study, the tumor-suppressive function of RNF31 in triple negative breast cancer (TNBC) was demonstrated. It was found that RNF31 could regulate the Hippo signaling pathway and its depletion increased TNBC cell proliferation and migration. Clinical data also showed that RNF31 expression was correlated with longer relapse-free survival in TNBC patients.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Francesca Biagioni, Ottavio Croci, Silvia Sberna, Elisa Donato, Arianna Sabo, Andrea Bisso, Laura Curti, Arianna Chiesa, Stefano Campaner
Summary: YAP functions as a master regulator of liver function by reshaping the enhancer landscape to control transcription of genes related to metabolism, proliferation, and inflammation. It antagonizes HNF4a, modulates immune infiltrate, and alters the vascular architecture of the liver to subvert lineage specification programs.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Oncology
Jeong-Yun Choi, Haeseung Lee, Eun-Ji Kwon, Hyeon-Joon Kong, Ok-Seon Kwon, Hyuk-Jin Cha
Summary: The study reveals a close correlation between elevated YAP expression and AXL expression in mesenchymal-type lung cancer, with doxorubicin treatment inducing YAP nuclear translocation in lung cancer cells, leading to AXL expression. The concurrent activation of TGF beta signaling coordinates YAP-dependent AXL expression through SMAD4, suggesting a promising target to improve chemosensitivity in mesenchymal-type lung cancer.
MOLECULAR ONCOLOGY
(2021)
Article
Biology
Yixiao Zhang, Lisha Sun, Haonan Li, Liping Ai, Qingtian Ma, Xinbo Qiao, Jie Yang, Hao Zhang, Xunyan Ou, Yining Wang, Guanglei Chen, Jinqi Xue, Xudong Zhu, Yu Zhao, Yongliang Yang, Caigang Liu
Summary: TLN1 overexpression contributes to TNBC metastasis and targeting the binding between TLN1 and integrin β1 may hold promise for TNBC treatment.
Review
Materials Science, Biomaterials
Thomas Lissek
Summary: Complex stimulation patterns can improve organ function and overall health, possibly leading to longer lifespans. This is achieved through activity-dependent transcriptional programs that remodel and adapt somatic cells, resembling younger cells. The cellular adaptation program targets aging-related processes, such as mitochondrial metabolism and cell-cell communication, resulting in functional improvements.
Article
Biology
Lizhi He, Henry Pratt, Mingshi Gao, Fengxiang Wei, Zhiping Weng, Kevin Struhl
Summary: YAP and TAZ are recruited by JUNB and STAT3 in addition to TEAD, and they interact with AP-1 proteins to stimulate transcriptional activation. Different classes of YAP/TAZ target sites are associated with distinct gene functions, and YAP-specific or TAZ-specific target sites have different sequence motifs and gene classes compared to shared YAP/TAZ target sites. Genes with YAP/TAZ sites of the AP-1 or TEAD class are linked to poor survival in breast cancer patients with triple-negative breast cancer.
Article
Pharmacology & Pharmacy
Li Yin, Zeping Fan, Peng Liu, Lanying Chen, Ziyi Guan, Yahui Liu, Yingying Luo
Summary: The study demonstrated that A3 can polarize macrophages into the M1 phenotype by activating the TLR4/NF-kappa B/MAPK signaling pathway, which represses breast tumorigenesis and progression.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Weerachai Singhatanadgit, Weerawan Hankamolsiri, Wanida Janvikul
Summary: The study showed that GGOH can counteract the negative effects of ZA on MSCs, preserving their viability and proliferation potential while promoting mineralization. GGOH prevented cell cycle arrest and apoptosis induced by ZA, and protected MSCs by reversing RhoA activity suppression and YAP activation. These findings suggest GGOH as a promising agent and YAP as a potential therapeutic target for MRONJ.
ROYAL SOCIETY OPEN SCIENCE
(2021)
Article
Cell Biology
Gwan-Jun Lee, Youn Ju Kim, Bongju Park, Sujin Yim, Chansang Park, Hyunsoo Roh, Yunwon Moon, Je Kyung Seong, Hyunsung Park
Summary: This study found that adipocytes are primarily responsible for the increase in Wnt5a levels in obesity. Adipocytes in subcutaneous white adipose tissues are more sensitive to high-fat diet and have a positive correlation between cell size and Wnt5a levels. YAP and TAZ activity responds to mechanical changes in hypertrophic adipocytes to promote Wnt5a expression.
CELL DEATH & DISEASE
(2022)
Article
Multidisciplinary Sciences
Thomas S. Postler, Vincent Peng, Dev M. Bhatt, Sankar Ghosh
Summary: Metformin, a first-line drug for type-2 diabetes mellitus, not only has anti-gluconeogenic and insulin-sensitizing properties, but also serves as a potent inhibitor of chronic inflammatory response of macrophages. Recent research has shown that metformin alters acute inflammatory response by activating AMP-activated protein kinase, independently of HIF1-alpha and IL-10, in primary macrophages and macrophage-like cell lines, suggesting a complex mechanism for its anti-inflammatory properties.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Yinxi Wang, Kimmo Kartasalo, Philippe Weitz, Balazs Acs, Masi Valkonen, Christer Larsson, Pekka Ruusuvuori, Johan Hartman, Mattias Rantalainen
Summary: The study demonstrated that deep learning analysis of transcriptome-wide expression morphology enables the prediction of mRNA expression and proliferation markers from routine histopathology whole slide images in breast cancer. This approach represents a significant advancement in predicting tumor molecular characteristics.
Article
Oncology
Anisha Ramessur, Bana Ambasager, Iker Valle Aramburu, Freddie Peakman, Kelly Gleason, Christoph Lehmann, Venizelos Papayannopoulos, Raoul Charles Coombes, Ilaria Malanchi
Summary: An elevated number of circulating neutrophils is a poor prognostic factor for breast cancer, and bone marrow activation is found to be involved. However, it is unclear how early this activation can be detected. In this study, we found subtype-specific changes in circulating neutrophils and perturbations in their overall kinase activity in newly diagnosed breast cancer patients. Different subtypes of breast cancer patients exhibited distinct neutrophil kinase activity patterns, and the lifespan of neutrophils also increased in cancer patients. These results suggest that the kinase activation patterns in circulating neutrophils may be used as markers to differentiate cancer patients from those with benign breast lesions.
BREAST CANCER RESEARCH
(2023)
Meeting Abstract
Oncology
Henry G. Withers, Ryan Ransom, Irwin H. Gelman
Article
Biochemistry & Molecular Biology
L. H. Higgins, H. G. Withers, A. Garbens, H. D. Love, L. Magnoni, S. W. Hayward, C. D. Moyes
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2009)
Article
Oncology
Julie McGrath, Louis Panzica, Ryan Ransom, Henry G. Withers, Irwin H. Gelman
MOLECULAR CANCER RESEARCH
(2019)
Article
Oncology
Masayuki Hagiwara, Atsushi Fushimi, Atrayee Bhattacharya, Nami Yamashita, Yoshihiro Morimoto, Mototsugu Oya, Henry G. Withers, Qiang Hu, Tao Liu, Song Liu, Kwok K. Wong, Mark D. Long, Donald Kufe
Summary: The oncogenic MUC1-C protein plays a crucial role in driving the dedifferentiation of castrate resistant prostate cancer cells. It activates the type II interferon-gamma (IFN-gamma) pathway and induces chromatin remodeling, leading to the suppression of immune response and promotion of cancer stem cell state.
Article
Oncology
Atsushi Fushimi, Yoshihiro Morimoto, Satoshi Ishikawa, Nami Yamashita, Atrayee Bhattacharya, Tatsuaki Daimon, Hasan Rajabi, Caining Jin, Masayuki Hagiwara, Yota Yasumizu, Zhou Luan, Wenhao Suo, Kwok-Kin Wong, Henry Withers, Song Liu, Mark D. Long, Donald Kufe
Summary: MUC1-C protein is activated in pulmonary epithelial cells and plays a crucial role in promoting the growth and development of small cell lung cancer (SCLC) cells through activation of the MYC pathway. Furthermore, the MUC1-C->MYC->NOTCH2 network is essential for self-renewal capacity and tumorigenicity of SCLC cells.
MOLECULAR CANCER RESEARCH
(2022)
Article
Oncology
Manmeet S. Ahluwalia, David A. Reardon, Ajay P. Abad, William T. Curry, Eric T. Wong, Sheila A. Figel, Laszlo L. Mechtler, David M. Peereboom, Alan D. Hutson, Henry G. Withers, Song Liu, Ahmed N. Belal, Jingxin Qiu, Kathleen M. Mogensen, Sanam S. Dharma, Andrew Dhawan, Meaghan T. Birkemeier, Danielle M. Casucci, Michael J. Ciesielski, Robert A. Fenstermaker
Summary: SurVaxM is a peptide vaccine that activates the immune system against glioblastoma cells. The combination of SurVaxM and adjuvant chemotherapy can extend the progression-free survival of newly diagnosed glioblastoma patients.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Nami Yamashita, Yoshihiro Morimoto, Atsushi Fushimi, Rehan Ahmad, Atrayee Bhattacharya, Tatsuaki Daimon, Naoki Haratake, Yuka Inoue, Satoshi Ishikawa, Masaaki Yamamoto, Tsuyoshi Hata, Sayuri Akiyoshi, Qiang Hu, Tao Liu, Henry Withers, Song Liu, Geoffrey I. Shapiro, Tomoharu Yoshizumi, Mark D. Long, Donald Kufe
Summary: In certain cancer cells, the chromatin remodeling complex SWI/SNF PBAF's subunit polybromo-1 (PBRM1) drives DNA damage resistance and immune evasion through unclear mechanisms. This study found that MUC1-C is necessary for PBRM1 expression in triple-negative breast cancer (TNBC) cells, and the two proteins form a nuclear complex. Transcriptional and chromatin accessibility analysis showed that MUC1-C and PBRM1 increase the expression of STAT1 and IRF1 by enhancing chromatin accessibility on their respective genes, as well as other genes involved in DNA damage resistance and immune evasion.
MOLECULAR CANCER RESEARCH
(2023)
Article
Multidisciplinary Sciences
Nami Yamashita, Henry Withers, Yoshihiro Morimoto, Atrayee Bhattacharya, Naoki Haratake, Tatsuaki Daimon, Atsushi Fushimi, Ayako Nakashoji, Aaron R. Thorner, Emily Isenhart, Spencer Rosario, Mark D. Long, Donald Kufe
Summary: Activation of MUC1-C protein is crucial for the development and state of TNBC CSCs, as it regulates self-renewal and oxidative phosphorylation inhibition by integrating activation of glycolytic pathway and repression of mtDNA genes. These findings have significant implications for understanding the pathogenesis and treatment of breast cancer.
Meeting Abstract
Oncology
Henry G. Withers, Irwin H. Gelman
Article
Chemistry, Medicinal
Zhimin Tao, Henry G. Withers, Harvey S. Penefsky, Jerry Goodisman, Abdul-Kader Souid
CHEMICAL RESEARCH IN TOXICOLOGY
(2006)