Article
Biochemistry & Molecular Biology
Leire Torices, Janire Mingo, Isabel Rodriguez-Escudero, Teresa Fernandez-Acero, Sandra Luna, Caroline E. Nunes-Xavier, Jose Lopez, Fatima Mercadillo, Maria Curras, Miguel Urioste, Maria Molina, Victor J. Cid, Rafael Pulido
Summary: Heterozygous germline mutations in PTEN gene are associated with hamartomas, tumors, and neurodevelopmental disorders. PTEN acts as a phosphatase, counteracting the pro-oncogenic function of PI3K. This study characterized several PTEN variants found in PHTS patients and observed complex patterns of loss of function, altered localization, and altered cleavage by caspase-3.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Zhaozhao Zhao, Qiushi Xu, Ran Wei, Leihuan Huang, Weixu Wang, Gang Wei, Ting Ni
Summary: This study shows that somatic SNVs near splice sites can lead to abnormal intronic polyadenylation (IPA), with some events overlapping with those triggered by snRNP inhibition. IPA-associated SNVs are enriched in tumor suppressor genes, providing a novel mechanism explaining the functional consequence of somatic SNVs in human cancer.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Oncology
Kunjian Lei, Min Luo, Zewei Tu, Shigang Lv, Junzhe Liu, Chuandong Gong, Minhua Ye, Miaojing Wu, Yilei Sheng, Xiaoyan Long, Jingying Li, Xingen Zhu, Kai Huang
Summary: This study systematically analyzed the expression and potential role of PAKs in human tumors. It found that high expression of PAKs is associated with poor prognosis in cancer patients. However, copy number variation, mutation, and DNA methylation of PAKs have limited impact on tumor development. The impact of PAKs on immunity varies with the type of tumor and tumor microenvironment. PAK1 and PAK4 may serve as stronger predictors of immune characteristics and potential targets for therapy. A PAK gene signature was identified as an independent prognostic factor for lower grade glioma and glioblastoma.
CANCER CELL INTERNATIONAL
(2022)
Article
Multidisciplinary Sciences
Nehakumari Maurya, Purvi Mohanty, Somprakash Dhangar, Purvi Panchal, Farah Jijina, S. Leo Prince Mathan, Chandrakala Shanmukhaiah, Manisha Madkaikar, Babu Rao Vundinti
Summary: This study investigated the relationship between genetic mutations in MDS patients and their survival and risk. The results showed that mutations in TP53, JAK2/3, KRAS, NRAS, and ASXL1 were associated with poor survival. The proposed M-IPSS-R system changed the risk stratification and could be useful in treatment planning.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Martina Pigoni, Ana Uzquiano, Bruna Paulsen, Amanda J. Kedaigle, Sung Min Yang, Panagiotis Symvoulidis, Xian Adiconis, Silvia Velasco, Rafaela Sartore, Kwanho Kim, Ashley Tucewicz, Sarah Yoshimi Tropp, Kalliopi Tsafou, Xin Jin, Lindy Barrett, Fei Chen, Edward S. Boyden, Aviv Regev, Joshua Z. Levin, Paola Arlotta
Summary: De novo heterozygous loss-of-function mutations in the PTEN gene have been found to affect specific cell types during human brain development and contribute to the occurrence of autism spectrum disorders. Using human cortical organoids from different donors, this study identified cell-type specific developmental events affected by PTEN mutations. The findings showed variations in developmental timing and abnormal neuronal activity caused by PTEN heterozygosity, which were influenced by the genetic background of the donors.
HUMAN MOLECULAR GENETICS
(2023)
Article
Genetics & Heredity
Bengi Ruken Yavuz, M. Kaan Arici, Habibe Cansu Demirel, Chung-Jung Tsai, Hyunbum Jang, Ruth Nussinov, Nurcan Tuncbag
Summary: Epidemiological studies show that individuals with neurodevelopmental disorders are more likely to develop certain types of cancer. While these disorders and cancer share proteins, pathways, and mutations, they differ in clinical outcomes. The key factor determining clinical outcome is signaling strength, with strong signaling promoting cell proliferation in cancer and moderate signaling affecting differentiation in neurodevelopmental disorders.
NPJ GENOMIC MEDICINE
(2023)
Article
Multidisciplinary Sciences
Motoki Ono, Tsutomu Miyamoto, Ryoichi Asaka, Junko Uchikawa, Hirofumi Ando, Yasuhiro Tanaka, Manaka Shinagawa, Yusuke Yokokawa, Shiho Asaka, Tian-Li Wang, Ie-Ming Shih, Tanri Shiozawa
Summary: This study aimed to create an EAOC mouse model by transplanting uterine pieces from donor mice, in which Arid1a and/or Pten was conditionally knocked out in endometrial cells, onto the ovarian surface or peritoneum of recipient mice. The results showed that induction of only Pten KO evoked atypical endometriosis, while induction of Arid1a; Pten double-KO evoked structures similar to EAOC. This mouse model provides a useful tool for investigating the mechanisms underlying the development of EAOC.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Sushmita Gordhandas, Eric Rios-Doria, Karen A. Cadoo, Amanda Catchings, Anna Maio, Yelena Kemel, Margaret Sheehan, Megha Ranganathan, Dina Green, Anjali Aryamvally, Angela G. Arnold, Erin Salo-Mullen, Beryl Manning-Geist, Tiffany Sia, Pier Selenica, Arnaud Da Cruz Paula, Chad Vanderbilt, Maksym Misyura, Mario M. Leitao, Jennifer J. Mueller, Vicky Makker, Maria Rubinstein, Claire F. Friedman, Qin Zhou, Alexia Iasonos, Alicia Latham, Maria Carlo, Yonina R. Murciano-Goroff, Marie Will, Michael F. Walsh, Shirin Issa Bhaloo, Lora H. Ellenson, Ozge Ceyhan-Birsoy, Michael F. Berger, Mark E. Robson, Nadeem Abu-Rustum, Carol Aghajanian, Kenneth Offit, Zsofia Stadler, Britta Weigelt, Diana L. Mandelker, Ying L. Liu
Summary: This study investigated the prevalence of germline pathogenic variants in patients with endometrial cancer, and found that 13% of patients had such variants, with 63% of high-penetrance genes exhibiting biallelic inactivation, potentially driving cancer development. The results support the importance of germline assessment in endometrial cancer for treatment and cancer prevention.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Article
Multidisciplinary Sciences
Majed Dasouki, Ayodeele Alaiya, Tanziel ElAmin, Zakia Shinwari, Dorota Monies, Mohamed Abouelhoda, Amjad Jabaan, Feras Almourfi, Zuhair Rahbeeni, Fahad Alsohaibani, Fahad Almohareb, Hazzaa Al-Zahrani, Francisco J. Guzman Vega, Stefan T. Arold, Mahmoud Aljurf, Syed Osman Ahmed
Summary: Autosomal recessive mutations in G6PC3 can lead to isolated and syndromic congenital neutropenia, which includes congenital heart disease and atypical inflammatory bowel disease. Comprehensive multi-omics analyses identified damaging effects of novel mutations in G6PC3 and MPL, as well as a unique molecular cytokine profile in patients with IBD. Liquid chromatography-mass spectrometry-based proteomics analysis revealed differential expression of key proteins linked to congenital heart disease and IBD in G6PC3-deficient plasma samples.
Article
Cell Biology
Haihui Zhong, Jie Wang, Yaru Zhu, Yefeng Shen
Summary: The study identified a prognostic risk model consisting of nine hub genes for LUAD, with high-risk patients having poor prognoses. The model serves as an independent prognostic factor for LUAD patients, and a nomogram was developed for prognostic prediction.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Ashitha S. Niranjana Murthy, Raviraj V. Suresh, B. Ramachandra Nallur
Summary: Research on the cancer and Autism Spectrum Disorders (ASD) gene PTEN has provided insights into the genotypic predictors of ASD-associated phenotypic outcomes. The study revealed increased mutational density in specific regions of PTEN, as well as the potential impact of certain SNPs on its dynamic stability. Additionally, variations in PTEN may trigger ASD manifestations.
Article
Pharmacology & Pharmacy
Yan Mao, Jinwen Xu, Xuejiao Xu, Jiayun Qiu, Zhengyun Hu, Feng Jiang, Guoping Zhou
Summary: Cellular senescence plays a critical role in carcinogenesis, development, and immunological regulation. This study identified a cellular senescence-related gene signature that can serve as a reliable predictor for clinical outcome and immunotherapeutic response in patients with acute myeloid leukemia.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Jun Xiao, Lingyan Zheng, Jingfeng Liu
Summary: This study systematically analyzed ferroptosis regulators in gastric cancer and identified three distinct subtypes of ferroptosis with different prognosis, hallmark pathway activity, and tumor-infiltrating immune cells. The quantification of ferroptosis levels based on prognostic signatures, along with the observed significant relationships between FPI and clinicopathological characteristics, suggests the potential of ferroptosis in guiding personalized treatment and predicting immune response.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Casey G. Langdon
Summary: Phosphatase and tensin homolog (PTEN) is a tumor-suppressive protein with phosphatase activity in both lipids and proteins. Its tumor-suppressive functions are lost through various mechanisms in different human malignancies. This review focuses on the changes in PTEN subcellular localization, its entry into the nucleus, and the impacts of disrupted PTEN nuclear localization on tumor promotion. Understanding the cytoplasmic and nuclear functions of PTEN is crucial in preventing human cancers.
Article
Immunology
Shaoran Song, Miao Zhang, Peiling Xie, Shuhong Wang, Yaochun Wang
Summary: This study reveals the importance of cuproptosis in breast cancer progression, prognosis, immune cell infiltration, and immunotherapy response. By developing a scoring system, we successfully quantify the cuproptosis pattern and construct a gene signature. Patients with low CRG scores show higher immune cell infiltration, immune checkpoint expression, immune checkpoint inhibitor scores, and greater sensitivity to immunotherapy. Furthermore, RAD23B is identified as a favorable target associated with breast cancer progression, drug resistance, and poor prognosis.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Microbiology
Gema Gonzalez-Rubio, Lucia Sastre-Vergara, Maria Molina, Humberto Martin, Teresa Fernandez-Acero
Summary: The cell wall integrity (CWI) MAPK pathway of budding yeast Saccharomyces cerevisiae plays a role in responding to cell wall damage and other stressful conditions. The activity of MAPK Slt2 drives the pathway's output by phosphorylating protein substrates, regulating their activity, stability, protein interaction, and subcellular localization. Further research is needed to fully understand the substrates of Slt2.
Article
Biochemistry & Molecular Biology
Elena Jimenez-Gutierrez, Teresa Fernandez-Acero, Esmeralda Alonso-Rodriguez, Maria Molina, Humberto Martin
Summary: The cell wall integrity pathway is a signaling pathway essential for yeast cell response to cell wall damage. By incorporating a genetic circuit as a signal amplifier, novel elements involved in this pathway can be identified. This study discovered various chemical agents, including neomycin, that can activate the pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Leire Torices, Janire Mingo, Isabel Rodriguez-Escudero, Teresa Fernandez-Acero, Sandra Luna, Caroline E. Nunes-Xavier, Jose Lopez, Fatima Mercadillo, Maria Curras, Miguel Urioste, Maria Molina, Victor J. Cid, Rafael Pulido
Summary: Heterozygous germline mutations in PTEN gene are associated with hamartomas, tumors, and neurodevelopmental disorders. PTEN acts as a phosphatase, counteracting the pro-oncogenic function of PI3K. This study characterized several PTEN variants found in PHTS patients and observed complex patterns of loss of function, altered localization, and altered cleavage by caspase-3.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Ines G. de Oya, Elena Jimenez-Gutierrez, Helene Gaillard, Maria Molina, Humberto Martin, Ralf Erik Wellinger
Summary: This study reveals the importance of oxidative and cell wall stress signaling in the response to manganese stress in yeast. Yap1 and Slt2 are both protective factors against manganese toxicity and oxidative stress. In mutants impaired in manganese detoxification, Yap1 depletion enhances Slt2 activation, suggesting an interplay between different stress signaling pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pathology
Caroline E. Nunes-Xavier, Maite Emaldi, Ingrid J. Guldvik, Hakon Ramberg, Kristin A. Tasken, Gunhild M. Maelandsmo, Oystein Fodstad, Roberto Llarena, Rafael Pulido, Jose I. Lopez
Summary: MVP is expressed in prostate cancer and positively correlated with biochemical recurrence, and it is also positively correlated with androgen receptor and immune checkpoint protein B7-H3, but not with PD-L1 or PTEN expression. MVP may play a significant role in immune regulation and drug resistance in prostate cancer.
PATHOLOGY RESEARCH AND PRACTICE
(2023)
Article
Oncology
Rafael Pulido, Caroline E. Nunes-Xavier
Summary: Neuroblastoma is a highly aggressive cancer in children with varying treatment outcomes. B7-H3 immune checkpoint protein is highly expressed in neuroblastoma and targeting it with immunotherapy has shown promising results.
TRANSLATIONAL ONCOLOGY
(2023)
Editorial Material
Cell Biology
Rafael Pulido, Caroline E. Nunes-Xavier
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Cell Biology
Wiljan J. A. J. Hendriks, Remco T. P. van Cruchten, Rafael Pulido
Summary: Protein tyrosine phosphatases and protein tyrosine kinases play important roles in controlling molecular signaling processes at cellular and organismal levels, affecting the quality of life. This review focuses on studying germline variants in the genes encoding the thirty-seven classical members of the protein tyrosine phosphatase superfamily. The results suggest a potential association between individual genes and specific disorders, highlighting the need for further research to establish a comprehensive genotype-phenotype map for this intriguing protein family.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Joana aniani Sa-Pessoa, Sara Lopez-Montesino, Kornelia Przybyszewska, Isabel Rodriguez-Escudero, Helina Marshall, Adelia Ova, Gunnar N. Schroeder, Peter Barabas, Maria Molina, Tim Curtis, Victor J. Cid, Jose A. Bengoechea
Summary: The trans-kingdom antimicrobial T6SS effector VgrG4 from Klebsiella pneumoniae can manipulate eukaryotic cells by altering the mitochondrial network. VgrG4 colocalizes with the endoplasmic reticulum protein mitofusin 2. VgrG4 induces the transfer of calcium from the endoplasmic reticulum to the mitochondria, activating the regulator of mitochondrial fission, Drp1, resulting in mitochondrial network fragmentation.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Marta Valenti, Maria Molina, Victor J. Cid
Summary: Gasdermin D (GSDMD) and mixed lineage kinase domain-like protein (MLKL) are pore-forming proteins involved in pyroptosis and necroptosis, respectively. By expressing GSDMD and its N-terminal domain (GSDMD(NT)) in yeast, they were found to inhibit yeast growth, induce mitochondrial fragmentation, and cause cell cycle arrest through TORC1 inhibition. They also disrupted endosomal and autophagic vesicular traffic. This study provides a humanized yeast platform for studying GSDMD and MLKL, which can be used for structure-function assays and drug discovery.
Article
Microbiology
Gema Gonzalez-Rubio, Humberto Martin, Maria Molina
Summary: This study demonstrates that the absence of Ptc1 protein phosphatase leads to the upregulation of the MAPK pathway and causes various functional defects in Saccharomyces cerevisiae. Additionally, it shows that the absence of Ptc1 also results in impaired mitochondrial inheritance and perturbed cell cycle progression, along with other physiological alterations including mitochondrial hyperpolarization and ROS accumulation.
MICROBIOLOGY SPECTRUM
(2023)
Editorial Material
Microbiology
Humberto Martin, Maria Molina