Ryan Titmas, MBA’s Post

This research by Rodriguez-Teja and colleagues uncovers a critical link between aging, basement membrane stiffness, and the development of prostate cancer. They discovered that as we age, the basement membrane surrounding prostate epithelial cells stiffens due to collagen crosslinking caused by advanced glycation end-products (AGEs). This stiffening is sensed by Endo180, a receptor found on epithelial cells, triggering a metabolic switch that favors OXPHOS, the process by which cells utilize oxygen for energy production. The study shows that this shift to OXPHOS promotes several cancer hallmarks, including increased proliferation, resistance to cell death, and invasiveness. The study utilizes Resipher, allowing for long-term, real-time measurements of oxygen consumption rates (OCR) using any media, to confirm that this increase in OXPHOS is directly linked to basement membrane stiffening. This finding highlights the relevance of Resipher for studying long-term metabolic changes in response to environmental cues, such as basement membrane stiffness. The authors demonstrate that Endo180 is crucial for this metabolic rewiring, and its role in promoting OXPHOS suggests it as a potential biomarker for early-stage prostate cancer. The study reveals a previously underappreciated mechanism by which the mechanical properties of the extracellular matrix can drive cellular metabolism and contribute to cancer development, opening new avenues for therapeutic interventions in prostate cancer. View it here: https://lnkd.in/ejpu6jNk #ProstateCancer #BasementMembraneStiffness #Endo180 #OXPHOS #Aging #CancerMetabolism #CancerBiomarkers

Plot twist: Asst Prof Sangmoo Jeong finds that rather than suppressing tumors like we thought, the E-cadherin protein actually promotes breast cancer growth by ramping up serine synthesis. This metabolic boost helps cancer cells grow and spread but could also provide a potential treatment target. By inhibiting an enzyme called PHGDH, Jeong and team were able to slow down cancer cells' internal serine factory. "E-Cadherin Induces Serine Synthesis to Support Progression and Metastasis of Breast Cancer” appears in Cancer Research. The implications extend beyond breast cancer - this metabolic mechanism might explain similar patterns in other E-cadherin-expressing cancers like ovarian and lung tumors. Initial testing shows that combining PHGDH inhibitors with existing chemotherapies could make treatments more effective while potentially requiring lower doses of harsh chemicals. Next, Jeong's lab plans to investigate whether blood serine levels could serve as an early warning system for detecting aggressive tumor growth. Co-authors: From Hopkins: Geonhui Lee, Claudia Wong, Anna Cho, Junior West, Ashleigh Crawford, Gabriella Russo, PhD, Bishwa Ranjan Si, Jungwoo Kim, Asst Prof Moonjung Jung, Robert Leone, Prof Andrew Ewald, Prof Konstantinos Konstantopoulos, Prof Denis Wirtz From UC Irvine: Lauren Hoffner, Asst Prof Cholsoon Jang #cancermetablism #metastasis #molecularbiology #biochemicalpathways #serinemetabolism #breastcancerresearch

Recent research highlights the critical role of OPA1 in maintaining mitochondrial dynamics, particularly in mitochondrial cristae structure and fusion. OPA1 exists in two primary forms: OPA1-L (long form), responsible for stabilizing mitochondrial cristae and promoting fusion, and OPA1-S (short form), generated through proteolytic cleavage and linked to fission processes. What's particularly noteworthy is that OPA1 overexpression has been identified as an unfavorable prognostic marker in various cancers, including breast, pancreatic, colorectal, gastric, and ovarian cancers. This overexpression is often associated with increased tumor aggressiveness and resistance to apoptosis. The mechanism behind this lies in OPA1's ability to help cancer cells maintain their mitochondrial integrity under stress, supporting survival and growth even in adverse conditions. While its role in mitochondrial fusion and cristae maintenance is well established, emerging studies are investigating whether OPA1 has additional functions. For instance, research suggests a possible involvement in mitophagy regulationand an impact on the integrated stress response (ISR), which could further promote cancer cell survival under metabolic stress. However, more studies are needed to fully understand the potential direct roles of OPA1 in processes beyond mitochondrial dynamics. Investigating OPA1 as a therapeutic target could open up new strategies for combating tumors that rely on mitochondrial resilience. #CancerResearch #OPA1 #MitochondrialDynamics #PrognosticMarkers #OncologyInnovation

#Cancer | Molecular #Mechanisms of #TumorNecrosisFactor Signalling via TNF-Receptors in the #TumorMicroEnvironment | OPEN ACCESS Review of the 'Ups & Downs' & How to Capitalise on for #Immunotherapy Boosts 👏 | Tumour necrosis factor (TNF) is a primary mediator of inflammatory processes by facilitating cell death, immune cell activation and triggering of inflammation. In the cancer context, research has revealed TNF as a multifaceted cytokine that can be both pro- or anti-tumorigenic depending on what context is observed. Here* Louisa Alim, Colm Keane & Fernando Guimaraes explore the plethora of ways that TNF and its receptors manipulate the functional and phenotypic characteristics in the tumour microenvironment (TME) on both tumour cells and immune cells, promoting either tumour elimination or progression. They discuss the latest cutting-edge TNF-focused biologics currently in clinical translation that modifies the TME to derive greater immune responses and therapeutic outcomes, and further give perspectives on the future of targeting TNF in the context of cancer by emerging technological approaches. *https://lnkd.in/erFEqEC6 Celentyx Ltd #immunooncology www.celentyx.com Professor Nicholas Barnes PhD, FBPhS Omar Qureshi Catherine Brady FIGURE | Anti-tumour and pro-tumour activities promoted by TNF signalling in the TME via TNFR1 and TNFR2 |

With exam season coming to an end I would like to share my poster presentation supervised by Sophia Semerdjieva, Nirusha Weerasinghe PhD, RSci, CBio, AFHEA, FIBMS at University of East London. It was based on the role of Hypoxia Inducible Factor–1α (HIF-1α) in the formation of vascular mimicry (VM) in high-grade and high-stage colorectal cancer. Key findings include: 🔬 Vascular Mimicry (VM): VM formation, where cancer cells develop blood vessel-like channels, is linked with aggressive tumors and poor prognosis. 🧬 Cell Line Studies: HCT116 cells, known for higher invasiveness and motility, demonstrated significant VM capability and elevated HIF-1α and EMT marker expression under hypoxic conditions. In contrast, HT29 cells showed a more epithelial phenotype with higher E-cadherin and Claudin-4 expression. ⚙️ Hypoxia’s Role: Hypoxic conditions were found to increase HIF-1α protein expression, promoting VM formation and correlating with aggressive cancer behavior. 🏥 Therapeutic Potential: Targeting the HIF-1α/EMT pathway could be a promising therapeutic approach for colorectal cancer metastasis. This research underscores the importance of understanding VM and EMT in colorectal cancer progression, opening doors for new therapeutic strategies. #ColorectalCancer #CancerResearch #Hypoxia #EMT #VascularMimicry #Oncology #HIF1α #CancerTherapy

New research demonstrating the potential of a novel fibroblast activation protein (FAP)-targeting CAR against #glioblastoma may lead to more effective treatments for malignant brain cancers. Congratulations to Wenbo Yu, Nga Truong, Michael P. Brown, and their team, for their important new research 📄 published in Clinical & Translational Immunology. The authors also highlighted the advantages of kinetic live-cell assays on Axion BioSystems’ Maestro Z analysis platform, which allowed the team to reveal biological mechanisms that may play a key 🔑 role in antitumor activity over time. According to the authors, “By using the novel Maestro Z instrument to track target cell destruction over several days, we allow CAR‐T cells the time required to be activated by CAR engagement and then deploy a range of cytotoxic mechanisms against antigen‐negative tumor cells.” Visit our website to learn more and discover how continuous, label-free monitoring on Maestro Z is accelerating the development of groundbreaking therapeutics. ➡️ https://bit.ly/4czfVP3 #cancerresearch #immunooncology

🚨 New Publication Alert! 🚨 Pleased to share the publication of our latest review article "Hypoxia as a critical player in extracellular vesicles-mediated intercellular communication between tumor cells and their surrounding microenvironment" at the Biochimica et Biophysica Acta (BBA) - Reviews on Cancer (Elsevier). 💡 This review explores the intricate role of extracellular vesicles (EVs) as pivotal mediators of intercellular communication, facilitating the transfer of bioactive molecules between tumor cells and their surrounding immune, endothelial, and stromal cell populations under low oxygen conditions. Additionally, the potential of hypoxia-targeting strategies in cancer clinical management is also addressed. 🔗 https://lnkd.in/dTbZvBXu Grateful to my supervising team for their guidance and support throughout the process. Cristina Xavier chiara riganti M. Helena Vasconcelos i3S - Instituto de Investigação e Inovação em Saúde Faculdade de Farmácia da Universidade do Porto Università degli Studi di Torino Dipartimento Biotecnologie Molecolari e Scienze per la Salute IMMUNO-model COST ACTION PANDORA CIG #cancerresearch #extracellularvesicles #tumormicroenvironment

Tumor suppressor forms gel-like assemblies to sacrifice cancer cells There are processes in the human body that can suppress the growth and proliferation of cancer cells. These mechanisms, including those involving the tumor suppressor protein p53, are widely studied due to their critical role in disease. Through studies of proteins that regulate p53, scientists have uncoupled a previously unrecognized tumor suppression mechanism. Usually found at low levels in cells, the p14 Alternative Reading Frame protein (p14ARF) is expressed at higher levels under oncogenic stress and activates p53. The researchers identified an alternative tumor suppression mechanism for p14ARF, showing how condensate formation and ribosome production disruption contribute to the process. The findings were published today in Nature Communications. The researchers demonstrated that increased expression of p14ARF causes the protein to phase separate with other cellular components. This occurs within the nucleolus, a membraneless compartment in the nucleus of cells responsible for ribosome production. In the nucleolus, p14ARF binds to and phase separates with nucleophosmin, an essential protein for ribosome production, creating a gel-like state, leading to decreased nucleophosmin dynamics, stalled ribosome biogenesis and cell toxicity. The process, kickstarted by p14ARF, thus represents a likely alternative tumor suppressive pathway. #ScienceMission #sciencenewshighlights https://lnkd.in/geT-dj9z

🚀 𝐍𝐞𝐰 𝐈𝐧𝐬𝐢𝐠𝐡𝐭𝐬 𝐢𝐧𝐭𝐨 𝐋𝐮𝐧𝐠 𝐀𝐝𝐞𝐧𝐨𝐜𝐚𝐫𝐜𝐢𝐧𝐨𝐦𝐚 (𝐋𝐔𝐀𝐃) 𝐏𝐫𝐨𝐠𝐫𝐞𝐬𝐬𝐢𝐨𝐧! 🌟 Recent research highlights the pivotal role of integrin β8 (ITGβ8) in lung adenocarcinoma (LUAD) by regulating macrophage polarization and tumor progression. Key findings include: ● 𝐏𝐫𝐨𝐠𝐧𝐨𝐬𝐭𝐢𝐜 𝐌𝐚𝐫𝐤𝐞𝐫: High ITGβ8 expression correlates with poor prognosis and increased tumor-associated macrophages (TAMs) in LUAD patients. ● 𝐌2 𝐏𝐨𝐥𝐚𝐫𝐢𝐳𝐚𝐭𝐢𝐨𝐧: ITGβ8 promotes the polarization of macrophages toward the M2 phenotype, which supports tumor growth and metastasis. ● 𝐂𝐂𝐋5 𝐒𝐞𝐜𝐫𝐞𝐭𝐢𝐨𝐧: ITGβ8 enhances CCL5 secretion in LUAD cells, attracting more M2-like macrophages into the tumor microenvironment. ● 𝐌𝐞𝐜𝐡𝐚𝐧𝐢𝐬𝐭𝐢𝐜 𝐏𝐚𝐭𝐡𝐰𝐚𝐲𝐬: The PI3K/AKT/IRF9 signaling pathway is crucial for ITGβ8's effects on CCL5 regulation and macrophage interaction. ● 𝐑𝐞𝐜𝐢𝐩𝐫𝐨𝐜𝐚𝐥 𝐑𝐞𝐠𝐮𝐥𝐚𝐭𝐢𝐨𝐧: M2-like macrophages produce IL8 and IL10, which further induce ITGβ8 expression in tumor cells, creating a feedback loop that drives tumor progression. This study underscores the complex interplay between LUAD cells and the immune microenvironment, revealing potential therapeutic targets to improve patient outcomes. #LungCancer #Oncology #CancerTherapy

Online!📌 Protein homeostasis maintained by HOOK1 levels promotes the tumorigenic and stemness properties of #ovariancancer cells through #reticulumstress and #autophagy --------------- Ovarian cancer has a high mortality rate mainly due to its resistance to currently used therapies. This resistance has been associated with the presence of cancer stem cells (CSCs), interactions with the microenvironment, and intratumoral heterogeneity. HOOK1 has been found to be transcriptionally altered in a substantial percentage of ovarian tumors, but its role in tumor initiation and development is still not fully understood. In this study, Amancio Carnero Moya observed that reducing the levels of HOOK1 in ovarian cancer cells reduced in vitro growth and migration and prevented tumor formation in vivo. Read here🧐 https://lnkd.in/dvxm8iUi #Stemness #Proteinhomeostasis IFO - Istituto Nazionale Tumori Regina Elena - Istituto Dermatologico San Gallicano