Article
Multidisciplinary Sciences
Johnny E. Elguero, Guangmei Liu, Katherine Tiemeyer, Shruthi Bandyadka, Heena Gandevia, Lauren Duro, Zhenhao Yan, Kimberly Mccall
Summary: This study found that Drosophila mutants lacking the phagocytic receptor Draper have phagocytic defects leading to neurodegenerative diseases. The study also discovered that phagocytic defects cause neurodegeneration through increased immune signaling.
Article
Cell Biology
Hugang Feng, Karen A. Lane, Theodoros Roumeliotis, Penny A. Jeggo, Navita Somaiah, Jyoti S. Choudhary, Jessica A. Downs
Summary: PBRM1 deficiency is associated with the response to immunotherapy in renal cancer, potentially through DNA damage-induced inflammatory signaling and maintenance of the G2/M checkpoint. The mutational status of PBRM1 can predict the response of renal cancer to immunotherapy.
GENES & DEVELOPMENT
(2022)
Article
Cell Biology
Xiaoling Zhang, Xianling Cong, Xiangting Jin, Yu'e Liu, Tong Zhang, Xinyuan Fan, Xiyao Shi, Xiaoying Zhang, Xue Wang, Yong-Guang Yang, Xiangpeng Dai
Summary: The transcription factor MYCN is frequently amplified and overexpressed in various cancers, and is considered undruggable. In this study, BRCA1-associated protein-1 (BAP1) is identified as an upstream regulator that stabilizes MYCN through direct binding. Depletion of BAP1 inhibits neuroblastoma tumor cell growth and migration, and confers cellular resistance to BET protein inhibitor JQ1 and Aurora A kinase inhibitor Alisertib. Our findings suggest that BAP1 could be a potential therapeutic target for MYCN-amplified neuroblastoma.
CELL DEATH & DISEASE
(2023)
Article
Oncology
Takahiro Hamoya, Gen Fujii, Yosuke Iizumi, Takumi Narita, Masami Komiya, Yui Matsuzawa, Kohei Miki, Tadashi Kondo, Shinji Kishimoto, Kenji Watanabe, Keiji Wakabayashi, Toshiyuki Sakai, Jiro Toshima, Michihiro Mutoh
Summary: Artesunate inhibits intestinal tumorigenesis by reducing the nuclear translocation of TCF/LEF transcription factors, thereby suppressing Wnt signaling.
Article
Oncology
Qun Zhao, Jian Guo, Guizhen Wang, Yun Bi, Xinran Cheng, Yingying Liao, Shu Jin, Lian Li, Yang Guo, Longrui Pan, Xudong Zhang, Yan Tan, Guangbiao Zhou, Xianjun Yu
Summary: This study revealed that the inhibition of CXCL13 in colorectal cancer has a mitigating effect on disease progression by promoting intestinal tumorigenesis through the activation of the AKT signaling pathway. Intestinal microbiota translocation drives CXCL13 production in dendritic cells through the activation of NF-kappa B signaling. Inhibition of microbiota translocation reduces CXCL13 production and ameliorates intestinal tumorigenesis.
Article
Oncology
Shanshan Sun, Jiali Shi, Xin Wang, Changgang Huang, Yuqian Huang, Jiayun Xu, Yuanyuan Jiang, Liying Cao, Tian Xie, Yongjie Wang, Zhihui Huang
Summary: Atractylon can inhibit proliferation and migration, as well as induce apoptosis in GBM cells by up-regulating SIRT3, suggesting it as a potential strategy for the treatment of GBM.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Article
Endocrinology & Metabolism
Yeonho Son, Cheoljun Choi, Abhirup Saha, Ji-Hyun Park, Hyeonyeong Im, Yoon Keun Cho, Je Kyung Seong, Rayanne B. Burl, Elizabeth A. Rondini, James G. Granneman, Yun-Hee Lee
Summary: REEP6 plays an important role in beta-adrenergic signal transduction in adipocytes, involving the expression and trafficking of Adcy3. Genetic inactivation of REEP6 reduces energy expenditure, increases adiposity, and enhances susceptibility to obesity-related metabolic dysfunction.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2022)
Article
Medicine, Research & Experimental
Hongzhong Zhou, Yiqun Du, Xiafei Wei, Chunli Song, Jianning Song, Nanson Xu, Weihong Huang, Lichan Chen, Fuwen Yao, Duanming Du, Chuanghua Qiu, Lihong Zhong, Yuchen Liu, Dayong Gu, Jin Wang, Yong Xu
Summary: This study found that DDX56 is upregulated in hepatocellular carcinoma (HCC) tissues and is strongly correlated with poor prognoses for HCC patients. DDX56 promotes HCC cell proliferation by interacting with MECOM to mono-methylate H3K9 on the MIST1 promoter. Furthermore, ZEB1 binds to DDX56 and transcriptionally activates DDX56, leading to HCC tumorigenesis.
Article
Chemistry, Medicinal
Manman Ji, Zhengrong Zhang, Feng Gao, Shaojie Yang, Juan Wang, Xuncui Wang, Guoqi Zhu
Summary: This study found that CUR can prevent behavioral changes and synaptic deficits induced by PTSD through activating the cAMP-PKA signaling pathway.
PHYTOTHERAPY RESEARCH
(2023)
Article
Cell Biology
Yandi Sun, Qian He, Jingjia Li, Ze Yang, Mashaal Ahmad, Yindan Lin, Di Wu, Lei Zheng, Jiangtao Li, Ben Wang, Chitty Chen, Yue Hu, Heng Luo, Yan Luo
Summary: This study found that lactate can inhibit the phosphorylation of G6PD by binding with GSTP1, thereby increasing the activity of G6PD and promoting the production of NADPH through PPP, enabling cancer cells to resist reactive oxygen species in glucose scarcity, indicating the important role of GSTP1 in tumor development as a lactate sensor.
CELL DEATH & DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Feng Tang, Hua Yu, Xia Wang, Jiageng Shi, Zhizhuang Chen, Hao Wang, Ziyu Wan, Qiqi Fu, Xuan Hu, Yisha Zuhaer, Tao Liu, Zhonghua Yang, Jianping Peng
Summary: NCAPG is overexpressed in bladder cancer, and its knockdown can inhibit cell proliferation through the inhibition of the NF-kappa B signaling pathway.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Raul Sanchez-Vazquez, Paula Martinez, Maria A. Blasco
Summary: This study demonstrates how extracellular signals can regulate telomere protection and length through modifications in TRF1 protein. Mutations in TRF1 lead to decreased telomere binding, increased DNA damage, accelerated telomere shortening, impaired response to proliferative signals, and decreased tumorigenesis potential. It highlights the role of PI3K/AKT pathway in regulating telomere maintenance and suggests potential targets for cancer therapy.
Article
Oncology
Kee-Beom Kim, Dong-Wook Kim, Youngchul Kim, Jun Tang, Nicole Kirk, Yongyu Gan, Bongjun Kim, Bingliang Fang, Jae-ll Park, Yi Zheng, Kwon-Sik Park
Summary: This study characterizes the activity of the WNT pathway in small cell lung cancer (SCLC) and identifies the key role of the WNT5A-RHOA axis in SCLC progression. It provides potential targets for therapeutic interventions and biomarkers to improve patient treatment.
Article
Immunology
Mahmoud Darweesh, Shady Younis, Zamaneh Hajikhezri, Arwa Ali, Chuan Jin, Tanel Punga, Soham Gupta, Magnus Essand, Leif Andersson, Goran Akusjarvi
Summary: ZC3H11A protein is involved in the regulation of NF-κB signaling pathway, and its depletion leads to enhanced signaling and accumulation defects of IκBα mRNA and protein.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Endocrinology & Metabolism
Natalia Lautherbach, Dawit A. P. Goncalves, Wilian A. Silveira, Silvia Paula-Gomes, Rafael Rossi Valentim, Neusa M. Zanon, Marcelo G. Pereira, Elen H. Miyabara, Luiz C. C. Navegantes, Isis C. Kettelhut
Summary: Ucn2 activates cAMP signaling and promotes muscle hypertrophy, protein synthesis, and signaling pathways, while decreasing atrogin-1 mRNA levels and protein degradation through lysosomal proteolytic activity inhibition. Ucn2 also induces a fiber type shift and improves fatigue muscle resistance. These findings suggest that Ucn2 triggers an anabolic and anti-catabolic response in skeletal muscle, potentially through the activation of cAMP cascade and participation of Akt and ERK1/2 signaling.
MOLECULAR METABOLISM
(2022)
Article
Medicine, Research & Experimental
Sanaz Jamalzadeh, Antti Hakkinen, Noora Andersson, Kaisa Huhtinen, Anna Laury, Sakari Hietanen, Johanna Hynninen, Jaana Oikkonen, Olli Carpen, Anni Virtanen, Sampsa Hautaniemi
Summary: RNA in situ hybridization (RNA-ISH) is a powerful technique for localizing and quantifying target RNA in individual cells. We have developed a comprehensive open-source tool called QuantISH for analyzing RNA-ISH images, which accurately classifies cancer cells and quantifies signal expression. Our results demonstrate that QuantISH is highly accurate and can be used to identify potential biomarkers.
LABORATORY INVESTIGATION
(2022)
Article
Multidisciplinary Sciences
Kaiyang Zhang, Erdogan Pekcan Erkan, Sanaz Jamalzadeh, Jun Dai, Noora Andersson, Katja Kaipio, Tarja Lamminen, Naziha Mansuri, Kaisa Huhtinen, Olli Carpen, Sakari Hietanen, Jaana Oikkonen, Johanna Hynninen, Anni Virtanen, Antti Hakkinen, Sampsa Hautaniemi, Anna Vaharautio
Summary: Chemotherapy resistance is a major contributor to cancer mortality, and a study focusing on high-grade serous ovarian cancer found that a stress-associated cell state consistently increased during chemotherapy, which was associated with poor progression-free survival.
Article
Biochemical Research Methods
Susanna Holmstrom, Sampsa Hautaniemi, Antti Hakkinen
Summary: In this study, a method called POIBM was proposed for batch correction in RNA sequencing. The method learns virtual reference samples directly from the data to correct batch effects without requiring prior phenotypic information. The results showed that POIBM outperforms or matches the performance of previous methods in various cancer datasets, effectively discovers true replicates, and improves cancer subtyping.
Article
Cell Biology
Juuli Raivola, Alice Dini, Hanna Karvonen, Emilia Piki, Kari Salokas, Wilhelmiina Niininen, Laura Kaleva, Kaiyang Zhang, Mariliina Arjama, Greta Gudoityte, Brinton Seashore-Ludlow, Markku Varjosalo, Olli Kallioniemi, Sampsa Hautaniemi, Astrid Murumagi, Daniela Ungureanu
Summary: In this study, PTK7 was identified as a potential therapeutic target in ovarian cancer. It was found to modulate cell adhesion and Rho-GTPase signaling, sustain epithelial-mesenchymal transition (EMT) and cell plasticity, and mediate aberrant Wnt signaling. Targeting PTK7 exhibited synergistic activity with chemotherapeutic agents and inhibitors in ovarian cancer, providing a new approach for its treatment.
CELL DEATH & DISEASE
(2022)
Article
Pharmacology & Pharmacy
Feng Deng, Maren Laasik, Liina Salminen, Lauri Lapatto, Kaisa Huhtinen, Yilin Li, Sampsa Hautaniemi, Johanna Hynninen, Mikko Niemi, Rainer Lehtonen
Summary: The study identified genetic variations in SLCO1B3, LIG3, GSTP1, ABCB1, and OPRM1 associated with risk of adverse effects, treatment response, and prognosis in patients receiving carboplatin-paclitaxel therapy for ovarian cancer.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Oncology
Alexandra Lahtinen, Kari Lavikka, Anni Virtanen, Yilin Li, Sanaz Jamalzadeh, Aikaterini Skorda, Anna Rossberg Lauridsen, Kaiyang Zhang, Giovanni Marchi, Veli-Matti Isoviita, Valeria Ariotta, Oskari Lehtonen, Taru A. Muranen, Kaisa Huhtinen, Olli Carpen, Sakari Hietanen, Wojciech Senkowski, Tuula Kallunki, Antti Hakkinen, Johanna Hynninen, Jaana Oikkonen, Sampsa Hautaniemi
Summary: Ovarian HGSC is often diagnosed at an advanced stage, with genetically diverse clones existing prior to treatment. This study analyzed whole-genome sequencing data from 510 samples of 148 HGSC patients, revealing three evolutionary states with distinct genomic features, pathways, and phenotypes, which showed significant association with treatment response. Pathway analysis suggested two potential evolutionary trajectories, and experiments with tumor organoids supported targeted therapy for tumors with enriched PI3K/AKT pathway. Heterogeneity analysis indicated more unique clones in samples from the site of origin compared to metastatic tumors or ascites. These findings highlight the importance of integrative tumor evolution analysis for identifying patient subtypes.
Article
Oncology
Sanna Pikkusaari, Manuela Tumiati, Anni Virtanen, Jaana Oikkonen, Yilin Li, Fernando Perez-Villatoro, Taru Muranen, Matilda Salko, Kaisa Huhtinen, Anna Kanerva, Heidi Koskela, Johanna Tapper, Riitta Koivisto-Korander, Titta Joutsiniemi, Ulla-Maija Haltia, Heini Lassus, Sampsa Hautaniemi, Anniina Farkkila, Johanna Hynninen, Sakari Hietanen, Olli Carpen, Liisa Kauppi
Summary: A clinically feasible assay was developed to identify HR-deficient tumors in high-grade serous ovarian cancers. The assay predicted clinical outcomes and helped determine which patients were most likely to benefit from platinum-based chemotherapy and PARP inhibitors.
CLINICAL CANCER RESEARCH
(2023)
Article
Cell Biology
Wojciech Senkowski, Laura Gall-Mas, Matias Marin Falco, Yilin Li, Kari Lavikka, Mette C. Kriegbaum, Jaana Oikkonen, Daria Bulanova, Elin J. Pietras, Karolin Vossgrone, Yan-Jun Chen, Erdogan Pekcan Erkan, Jun Dai, Anastasia Lundgren, Mia Kristine Gronning Hog, Ida Marie Larsen, Tarja Lamminen, Katja Kaipio, Jutta Huvila, Anni Virtanen, Lars Engelholm, Pernille Christiansen, Eric Santoni-Rugiu, Kaisa Huhtinen, Olli Carpen, Johanna Hynninen, Sampsa Hautaniemi, Anna Vaharautio, Krister Wennerberg
Summary: This article describes a method for culturing organoids from high-grade serous ovarian cancer (HGSC) with improved efficacy compared to previous reports (53% vs. 23%-38%). The organoids recapitulated genetic and phenotypic features of the original tumors. The organoid drug responses correlated with clinical treatment outcomes, but only in organoids maintained in human plasma-like medium. This resource facilitates the application of HGSC organoids in ovarian cancer research.
DEVELOPMENTAL CELL
(2023)
Article
Cell Biology
Liangru Fei, Kaiyang Zhang, Nikita Poddar, Sampsa Hautaniemi, Biswajyoti Sahu
Summary: The transition from mesenchymal fibroblast identity to epithelial pancreatic exocrine fate involves two deterministic steps, which are the activation of HHEX with FOXA2 and SOX17 to define an endodermal progenitor state, and the temporary activation of GATA4 essential for the maintenance of pancreatic cell fate program.
DEVELOPMENTAL CELL
(2023)
Article
Cell Biology
Emilia Piki, Alice Dini, Juuli Raivola, Kari Salokas, Kaiyang Zhang, Markku Varjosalo, Teijo Pellinen, Katja Valimaki, Kristina Tabor Veskimae, Synnove Staff, Sampsa Hautaniemi, Astrid Murumagi, Daniela Ungureanu
Summary: Dysregulation of the Wnt pathway, specifically the expression of the non-canonical receptor ROR1, is linked to ovarian cancer progression and drug resistance. ROR1 expression is enhanced by neoadjuvant chemotherapy, and its interaction with Wnt5a activates oncogenic signaling pathways in ovarian cancer cells. Furthermore, ROR1 and its downstream effector STAT3 are expressed at higher levels in stromal cells than in epithelial cancer cells in ovarian cancer tumors.
CELL DEATH DISCOVERY
(2023)
Article
Biochemical Research Methods
Aikaterini Skorda, Anna Rossberg Lauridsen, Kaisa Huhtinen, Alexandra Lahtinen, Wojciech Senkowski, Jaana Oikkonen, Johanna Hynninen, Sampsa Hautaniemi, Tuula Kallunki
Summary: Patient-derived organoids (PDOs) are ideal ex vivo model systems for studying cancer progression and drug resistance mechanisms. This study presents a protocol for measuring drug efficacy in three-dimensional (3D) high-grade serous ovarian cancer PDO cultures through quantification of cytotoxicity and analyzing proliferation using the Ki67 biomarker.
Article
Medicine, Research & Experimental
Mai T. N. Nguyen, Anna Rajavuori, Kaisa Huhtinen, Sakari Hietanen, Johanna Hynninen, Jaana Oikkonen, Sampsa Hautaniemi
Summary: Circulating tumor DNA (ctDNA) analysis is a promising tool for detecting and profiling cancer genomics changes. However, copy-number analysis for treatment effect monitoring has received less attention compared to mutations. Our study shows that copy-number analysis using a sequencing panel can detect consistent profiles even in low-tumor content ctDNA samples. Longitudinal analysis reveals changes in copy-number profiles in high-tumor content plasma samples, suggesting a relationship between copy-number alterations and relapse. These findings highlight the importance of genomic profiling during treatment.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Meeting Abstract
Environmental Sciences
Liisa Kauppi, Sanna Pikkusaari, Manuela Tumiati, Anni Virtanen, Taru Muranen, Jaana Oikkonen, Yilin Li, Sampsa Hautaniemi, Fernando Perez, Anniina Farkkila, Johanna Hynninen, Sakari Hietanen, Olli Carpen
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
(2022)
Meeting Abstract
Oncology
Alexandra Lahtinen, Kari Lavikka, Yilin Li, Sanaz Jamalzadeh, Anni Virtanen, Rainer Lehtonen, Olli Carpen, Sakari Hietanen, Kaisa Huhtinen, Antti Hakkinen, Johanna Hynninen, Jaana Oikkonen, Sampsa Hautaniemi
Meeting Abstract
Pharmacology & Pharmacy
F. Deng, M. Laasik, L. Salminen, L. Lapatto, K. Huhtinen, Y. Li, S. Hautaniemi, J. Hynninen, M. Niemi, R. Lehtonen
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
(2022)