Biochimie最新文献_第7页

Galactokinase-like protein from Leishmania donovani: Biochemical and structural characterization of a recombinant protein 唐氏利什曼原虫的半乳糖激酶样蛋白：重组蛋白的生化和结构鉴定

IF 3.9 3区生物学

Biochimie Pub Date : 2024-04-04 DOI: 10.1016/j.biochi.2024.03.017

Hasana Baber , Arega Aghajani , B. Harold Gallimore , Cassandra Bethel , James G. Hyatt , Elizabeth F.B. King , Helen P. Price , Marissa L. Maciej-Hulme , Suat Sari , Anja Winter

{"title":"Galactokinase-like protein from Leishmania donovani: Biochemical and structural characterization of a recombinant protein","authors":"Hasana Baber , Arega Aghajani , B. Harold Gallimore , Cassandra Bethel , James G. Hyatt , Elizabeth F.B. King , Helen P. Price , Marissa L. Maciej-Hulme , Suat Sari , Anja Winter","doi":"10.1016/j.biochi.2024.03.017","DOIUrl":"https://doi.org/10.1016/j.biochi.2024.03.017","url":null,"abstract":"<div><p>Leishmaniasis is a spectrum of conditions caused by infection with the protozoan <em>Leishmania</em> spp. parasites. Leishmaniasis is endemic in 98 countries around the world, and resistance to current anti-leishmanial drugs is rising. Our work has identified and characterised a previously unstudied galactokinase-like protein (GalK) in <em>Leishmania donovani</em>, which catalyses the MgATP-dependent phosphorylation of the C-1 hydroxyl group of <span>d</span>-galactose to galactose-1-phosphate. Here, we report the production of the catalytically active recombinant protein in <em>E. coli</em>, determination of its substrate specificity and kinetic constants, as well as analysis of its molecular envelope using <em>in solution</em> X-ray scattering. Our results reveal kinetic parameters in range with other galactokinases with an average apparent Km value of 76 μM for galactose, V<sub>max</sub> and apparent K<sub>cat</sub> values with 4.46376 × 10<sup>−9</sup> M/s and 0.021 s<sup>−1</sup>, respectively. Substantial substrate promiscuity was observed, with galactose being the preferred substrate, followed by mannose, fructose and GalNAc. <em>Ld</em>GalK has a highly flexible protein structure suggestive of multiple conformational states in solution, which may be the key to its substrate promiscuity. Our data presents novel insights into the galactose salvaging pathway in <em>Leishmania</em> and positions this protein as a potential target for the development of pharmaceuticals seeking to interfere with parasite substrate metabolism.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140536810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multifunctional host-defense peptides isolated from skin secretions of the banana tree dwelling frog Boana platanera (Hylidae; Hylinae) 从香蕉树栖蛙 Boana platanera (Hylidae; Hylinae) 皮肤分泌物中分离出的多功能宿主防御肽。

IF 3.9 3区生物学

Biochimie Pub Date : 2024-03-30 DOI: 10.1016/j.biochi.2024.03.012

J. Michael Conlon , Ananyaa Sridhar , Dawood Khan , Taylor S. Cunning , Jack J. Delaney , Megan G. Taggart , Nigel G. Ternan , Jérôme Leprince , Laurent Coquet , Thierry Jouenne , Samir Attoub , Milena Mechkarska

{"title":"Multifunctional host-defense peptides isolated from skin secretions of the banana tree dwelling frog Boana platanera (Hylidae; Hylinae)","authors":"J. Michael Conlon , Ananyaa Sridhar , Dawood Khan , Taylor S. Cunning , Jack J. Delaney , Megan G. Taggart , Nigel G. Ternan , Jérôme Leprince , Laurent Coquet , Thierry Jouenne , Samir Attoub , Milena Mechkarska","doi":"10.1016/j.biochi.2024.03.012","DOIUrl":"10.1016/j.biochi.2024.03.012","url":null,"abstract":"<div><p>Five host-defense peptides (figainin 2PL, hylin PL, raniseptin PL, plasticin PL, and peptide YL) were isolated from norepinephrine-stimulated skin secretions of the banana tree dwelling frog <em>Boana platanera</em> (Hylidae; Hylinae) collected in Trinidad.</p><p>Raniseptin PL (GVFDTVKKIGKAVGKFALGVAKNYLNS.NH<sub>2</sub>) and figainin 2PL (FLGTVLKLGKAIAKTVVPMLTNAMQPKQ. NH<sub>2</sub>) showed potent and rapid bactericidal activity against a range of clinically relevant Gram-positive and Gram-negative ESKAPE <sup>+</sup> pathogens and <em>Clostridioides difficile.</em> The peptides also showed potent cytotoxic activity (LC<sub>50</sub> values < 30 μM) against A549, MDA-MB-231 and HT29 human tumor-derived cell lines but appreciably lower hemolytic activity against mouse erythrocytes (LC<sub>50</sub> = 262 ± 14 μM for raniseptin PL and 157 ± 16 μM for figainin 2PL). Hylin PL (FLGLIPALAGAIGNLIK.NH<sub>2</sub>) showed relatively weak activity against microorganisms but was more hemolytic. The glycine-leucine-rich peptide with structural similarity to the plasticins (GLLSTVGGLVGGLLNNLGL.NH<sub>2</sub>) and the non-cytotoxic peptide YL (YVPGVIESLL.NH<sub>2</sub>) lacked antimicrobial and cytotoxic activities. Hylin PL, raniseptinPL and peptide YL stimulated the rate of release of insulin from BRIN-BD11 clonal β-cells at concentrations ≥100 nM. Peptide YL was the most effective (2.3-fold increase compared with basal rate at 1 μM concentration) and may represent a template for the design of a new class of incretin-based anti-diabetic drugs.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300908424000701/pdfft?md5=0e62b58f0bacba03f8bb7c5ea584abbd&pid=1-s2.0-S0300908424000701-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140338045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of ozone therapy on mouse liver mitochondrial function and antioxidant system 臭氧疗法对小鼠肝脏线粒体功能和抗氧化系统的影响

IF 3.9 3区生物学

Biochimie Pub Date : 2024-03-26 DOI: 10.1016/j.biochi.2024.03.014

Maria M. Oliveira , Sofia Correia , Cecilia Peirone , Marques Magalhães , Paula Oliveira , Francisco Peixoto

{"title":"Impact of ozone therapy on mouse liver mitochondrial function and antioxidant system","authors":"Maria M. Oliveira , Sofia Correia , Cecilia Peirone , Marques Magalhães , Paula Oliveira , Francisco Peixoto","doi":"10.1016/j.biochi.2024.03.014","DOIUrl":"10.1016/j.biochi.2024.03.014","url":null,"abstract":"<div><p>Ozone therapy's efficacy might stem from the regulated and mild oxidative stress resulting from ozone's interactions with various biological elements. The present work aimed to characterize the hepatic mitochondrial response to ozone treatment and its relationship with the antioxidant system response. Two groups of mice were used: one control group and another injected intraperitoneally with an O<sub>3</sub>/O<sub>2</sub> mixture (80 ml/kg) for 5 days. Mitochondrial respiration supported by different substrates was significantly inhibited, as well as complexes I and II/III, but not complex IV. The analysis of the electron transport chain complex activity showed significant inhibitions in complexes I and II/III but not in complex IV. These inhibitions can prevent mitochondrial reactive oxygen species (ROS) production. Additionally, there was a decline in glutathione content, unaccompanied by a rise in its oxidized form. The ozone-treated groups showed a significant increase in the activity of superoxide dismutase and glutathione peroxidase, while catalase and glutathione reductase experienced no significant alterations. Adenine nucleotides increased in the ozone group, but only the increase in adenosine diphosphate is significant, so the cell's energy charge is unaffected. This study shows that mitochondria may play a crucial role in ozone treatment. However, it also highlights the need for further studies to understand the molecular mechanism.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300908424000725/pdfft?md5=ec8fe957fe9a87be5067c6dab43ed873&pid=1-s2.0-S0300908424000725-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140320056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The impact of chemotherapy on adipose tissue remodeling: The molecular players involved in this tissue wasting 化疗对脂肪组织重塑的影响：参与组织损耗的分子角色。

IF 3.9 3区生物学

Biochimie Pub Date : 2024-03-26 DOI: 10.1016/j.biochi.2024.03.016

Samuel Barbosa , Mafalda Barbosa Pedrosa , Rita Ferreira , Daniel Moreira-Gonçalves , Lúcio Lara Santos

{"title":"The impact of chemotherapy on adipose tissue remodeling: The molecular players involved in this tissue wasting","authors":"Samuel Barbosa , Mafalda Barbosa Pedrosa , Rita Ferreira , Daniel Moreira-Gonçalves , Lúcio Lara Santos","doi":"10.1016/j.biochi.2024.03.016","DOIUrl":"10.1016/j.biochi.2024.03.016","url":null,"abstract":"<div><p>The depletion of visceral and subcutaneous adipose tissue (AT) during chemotherapy significantly correlates with diminished overall survival and progression-free survival. Despite its clinical significance, the intricate molecular mechanisms governing this AT loss and its chemotherapy-triggered initiation remain poorly understood. Notably, the evaluation of AT remodeling in most clinical trials has predominantly relied on computerized tomography scans or bioimpedance, with molecular studies often conducted using animal or in vitro models. To address this knowledge gap, a comprehensive narrative review was conducted. The findings underscore that chemotherapy serves as a key factor in inducing AT loss, exacerbating cachexia, a paraneoplastic syndrome that significantly compromises patient quality of life and survival. The mechanism driving AT loss appears intricately linked to alterations in AT metabolic remodeling, marked by heightened lipolysis and fatty acid oxidation, coupled with diminished lipogenesis. However, adipocyte stem cells' lost ability to divide due to chemotherapy also appears to be at the root of the loss of AT. Notably, chemotherapy seems to deactivate the mitochondrial antioxidant system by reducing key regulatory enzymes responsible for neutralizing reactive oxygen species (ROS), thereby impeding lipogenesis. Despite FDG-PET evidence of AT browning, no molecular evidence of thermogenesis was reported. Prospective investigations unraveling the molecular mechanisms modulated in AT by chemotherapy, along with therapeutic strategies aimed at preventing AT loss, promise to refine treatment paradigms and enhance patient outcomes.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300908424000749/pdfft?md5=058b3ddc3df668c738a551bf6c562da4&pid=1-s2.0-S0300908424000749-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140308294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of soluble epoxide hydrolase as a therapeutic approach for blood-brain barrier dysfunction 将抑制可溶性环氧化物水解酶作为治疗血脑屏障功能障碍的一种方法。

IF 3.9 3区生物学

Biochimie Pub Date : 2024-03-24 DOI: 10.1016/j.biochi.2024.03.015

Shuo Li, Huijia Song, Yanping Sun, Yongjun Sun, Huimin Zhang, Zibin Gao

{"title":"Inhibition of soluble epoxide hydrolase as a therapeutic approach for blood-brain barrier dysfunction","authors":"Shuo Li, Huijia Song, Yanping Sun, Yongjun Sun, Huimin Zhang, Zibin Gao","doi":"10.1016/j.biochi.2024.03.015","DOIUrl":"10.1016/j.biochi.2024.03.015","url":null,"abstract":"<div><p>The blood-brain barrier (BBB) is a protective semi-permeable structure that regulates the exchange of biomolecules between the peripheral blood and the central nervous system (CNS). Due to its specialized tight junctions and low vesicle trafficking, the BBB strictly limits the paracellular passage and transcellular transport of molecules to maintain the physiological condition of brain tissues. BBB breakdown is associated with many CNS disorders. Soluble epoxide hydrolase (sEH) is a hydrolase enzyme that converts epoxy-fatty acids (EpFAs) to their corresponding diols and is involved in the onset and progression of multiple diseases. EpFAs play a protective role in the central nervous system via preventing neuroinflammation, making sEH a potential therapeutic target for CNS diseases. Recent studies showed that sEH inhibition prevented BBB impairment caused by stroke, hemorrhage, traumatic brain injury, hyperglycemia and sepsis via regulating the expression of tight junctions. In this review, the protective actions of sEH inhibition on BBB and potential mechanisms are summarized, and some important questions that remain to be resolved are also addressed.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Melatonin facts: Melatonin lacks immuno-inflammation boosting capacities at the molecular and cellular levels 褪黑素的事实：褪黑素在分子和细胞水平上缺乏促进免疫炎症的能力。

IF 3.9 3区生物学

Biochimie Pub Date : 2024-03-18 DOI: 10.1016/j.biochi.2024.03.010

Jean A. Boutin , Valérie Hamon de Almeida , Nathalie Coussay , Céline Legros , Gilles Ferry , Karine Reybier

引用次数: 0

The mutual and dynamic role of TSPO and ligands in their binding process: An example with PK-11195 TSPO 和配体在其结合过程中的相互和动态作用：以 PK-11195 为例。

IF 3.3 3区生物学

Biochimie Pub Date : 2024-03-16 DOI: 10.1016/j.biochi.2024.03.009

{"title":"The mutual and dynamic role of TSPO and ligands in their binding process: An example with PK-11195","authors":"","doi":"10.1016/j.biochi.2024.03.009","DOIUrl":"10.1016/j.biochi.2024.03.009","url":null,"abstract":"<div><p>Translocator protein (TSPO) is an 18 kDa transmembrane protein, localized primarily on the outer mitochondrial membrane. It has been found to be involved in various physiological processes and pathophysiological conditions. Though studies on its structure have been performed only recently, there is little information on the nature of dynamics and doubts about some structures referenced in the literature, especially the NMR structure of mouse TSPO. In the present work, we thoroughly study the dynamics of mouse TSPO protein by means of atomistic molecular dynamics simulations, in presence as well as in absence of the diagnostic ligand PKA. We considered two starting structures: the NMR structure and a homology model (HM) generated on the basis of X-ray structures from bacterial TSPO. We examine the conformational landscape in both the modes for both starting points, in presence and absence of the ligand, in order to measure its impact for both structures. The analysis highlights high flexibility of the protein globally, but NMR simulations show a surprisingly flexibility even in the presence of the ligand. Interestingly, this is not the case for HM calculations, to the point that the ligand seems not so stable as in the NMR system and an unbinding event process is partially sampled. All those results tend to show that the NMR structure of mTSPO seems not deficient but is just in another portion of the global conformation space of TSPO.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300908424000671/pdfft?md5=b7784e0a84b2e69202dea04a8e4b84c0&pid=1-s2.0-S0300908424000671-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140144834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The multifaceted role of proteases and modern analytical methods for investigation of their catalytic activity 蛋白酶的多方面作用以及研究其催化活性的现代分析方法。

IF 3.9 3区生物学

Biochimie Pub Date : 2024-03-15 DOI: 10.1016/j.biochi.2024.03.006

Tatiana A. Filippova , Rami A. Masamrekh , Yulia Yu. Khudoklinova , Victoria V. Shumyantseva , Alexey V. Kuzikov

{"title":"The multifaceted role of proteases and modern analytical methods for investigation of their catalytic activity","authors":"Tatiana A. Filippova , Rami A. Masamrekh , Yulia Yu. Khudoklinova , Victoria V. Shumyantseva , Alexey V. Kuzikov","doi":"10.1016/j.biochi.2024.03.006","DOIUrl":"10.1016/j.biochi.2024.03.006","url":null,"abstract":"<div><p>We discuss the diverse functions of proteases in the context of their biotechnological and medical significance, as well as analytical approaches used to determine the functional activity of these enzymes. An insight into modern approaches to studying the kinetics and specificity of proteases, based on spectral (absorption, fluorescence), mass spectrometric, immunological, calorimetric, and electrochemical methods of analysis is given. We also examine in detail electrochemical systems for determining the activity and specificity of proteases. Particular attention is given to exploring innovative electrochemical systems based on the detection of the electrochemical oxidation signal of amino acid residues, thereby eliminating the need for extra redox labels in the process of peptide synthesis. In the review, we highlight the main prospects for the further development of electrochemical systems for the study of biotechnologically and medically significant proteases, which will enable the miniaturization of the analytical process for determining the catalytic activity of these enzymes.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140144833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unraveling the impact of the p.R107L mutation on the structure and function of human αB-Crystallin: Implications for cataract formation 揭示 p.R107L 突变对人类 αB-Crystallin 结构和功能的影响：对白内障形成的影响。

IF 3.9 3区生物学

Biochimie Pub Date : 2024-03-15 DOI: 10.1016/j.biochi.2024.03.004

Farid Nasiri , Parisa Ebrahimi , Mohammad Bagher Shahsavani , Anis Barati , Issa Zarei , Jun Hong , Masaru Hoshino , Ali Akbar Moosavi-Movahedi , Reza Yousefi

{"title":"Unraveling the impact of the p.R107L mutation on the structure and function of human αB-Crystallin: Implications for cataract formation","authors":"Farid Nasiri , Parisa Ebrahimi , Mohammad Bagher Shahsavani , Anis Barati , Issa Zarei , Jun Hong , Masaru Hoshino , Ali Akbar Moosavi-Movahedi , Reza Yousefi","doi":"10.1016/j.biochi.2024.03.004","DOIUrl":"10.1016/j.biochi.2024.03.004","url":null,"abstract":"<div><p>To date, several pathogenic mutations have been identified in the primary structure of human α-Crystallin, frequently involving the substitution of arginine with a different amino acid. These mutations can lead to the incidence of cataracts and myopathy. Recently, an important cataract-associated mutation has been reported in the functional α-Crystallin domain (ACD) of human αB-Crystallin protein, where arginine 107 (R107) is replaced by a leucine. In this study, we investigated the structure, chaperone function, stability, oligomerization, and amyloidogenic properties of the p.R107L human αB-Crystallin using a number of different techniques. Our results suggest that the p.R107L mutation can cause significant changes in the secondary, tertiary, and quaternary structures of αB-Crystallin. This cataractogenic mutation led to the formation of protein oligomers with larger sizes than the wild-type protein and reduced the chemical and thermal stability of the mutant chaperone. Both fluorescence and microscopic assessments indicated that this mutation significantly altered the amyloidogenic properties of human αB-Crystallin. Furthermore, the mutant protein indicated an attenuated <em>in vitro</em> chaperone activity. The molecular dynamics (MD) simulation confirmed the experimental results and indicated that p.R107L mutation could alter the proper conformation of human αB-Crystallin dimers. In summary, our results indicated that the p.R107L mutation could promote the formation of larger oligomers, diminish the stability and chaperone activity of human αB-Crystallin, and these changes, in turn, can play a crucial role in the development of cataract disorder.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140144835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The molecular crosstalk of the hippo cascade in breast cancer: A potential central susceptibility 乳腺癌中希波级联的分子串联：潜在的中心易感性。

IF 3.9 3区生物学

Biochimie Pub Date : 2024-03-15 DOI: 10.1016/j.biochi.2024.03.008

Sulfath Thottungal Parambil, Gisha Rose Antony, Ajeesh Babu Littleflower, Lakshmi Subhadradevi

{"title":"The molecular crosstalk of the hippo cascade in breast cancer: A potential central susceptibility","authors":"Sulfath Thottungal Parambil, Gisha Rose Antony, Ajeesh Babu Littleflower, Lakshmi Subhadradevi","doi":"10.1016/j.biochi.2024.03.008","DOIUrl":"10.1016/j.biochi.2024.03.008","url":null,"abstract":"<div><p>The incidence of breast cancer is perpetually growing globally, and it remains a major public health problem and the leading cause of mortality in women. Though the aberrant activities of the Hippo pathway have been reported to be associated with cancer, constructive knowledge of the pathway connecting the various elements of breast cancer remains to be elucidated. The Hippo transducers, yes-associated protein (YAP) and transcriptional co-activator with PDZ binding motif (TAZ), are reported to be either tumor suppressors, oncogenes, or independent prognostic markers in breast cancer. Thus, there is further need for an explicative evaluation of the dilemma with this molecular contribution of Hippo transducers in modulating breast malignancy. In this review, we summarize the intricate crosstalk of the Hippo pathway in different aspects of breast malignancy, including stem-likeness, cellular signaling, metabolic adaptations, tumor microenvironment, and immune responses. The collective data shows that Hippo transducers play an indispensable role in mammary tumor formation, progression, and dissemination. However, the cellular functions of YAP/TAZ in tumorigenesis might be largely dependent on the mechanical and biophysical cues they interact with, as well as on the cell phenotype. This review provides a glimpse into the plausible biological contributions of the cascade to the inward progression of breast carcinoma and suggests potential therapeutic prospects.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140144832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0