Mechanism insights and therapeutic intervention of tumor metastasis: latest developments and perspectives

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 2, 2024

Abstract Metastasis remains a pivotal characteristic of cancer and is the primary contributor to cancer-associated mortality. Despite its significance, mechanisms governing metastasis are not fully elucidated. Contemporary findings in domain biology have shed light on molecular aspects this intricate process. Tumor cells undergoing invasion engage with other cellular entities proteins en route their destination. Insights into these engagements enhanced our comprehension principles directing movement adaptability metastatic cells. The tumor microenvironment plays role facilitating proliferation by enabling navigate through stromal barriers. Such attributes influenced genetic epigenetic changes occurring surrounding milieu. A profound understanding process’s biological indispensable for devising efficacious therapeutic strategies. This review delves recent developments concerning metastasis-associated genes, important signaling pathways, microenvironment, metabolic processes, peripheral immunity, mechanical forces metastasis. In addition, we combine advances particular emphasis prospect developing effective interventions including most popular immunotherapies nanotechnology combat We also identified limitations current research metastasis, encompassing drug resistance, restricted animal models, inadequate biomarkers early detection methods, as well heterogeneity among others. It anticipated that comprehensive will significantly contribute advancement research.

Language: Английский

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The significant role of amino acid metabolic reprogramming in cancer

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 29, 2024

Amino acid metabolism plays a pivotal role in tumor microenvironment, influencing various aspects of cancer progression. The metabolic reprogramming amino acids cells is intricately linked to protein synthesis, nucleotide modulation signaling pathways, regulation cell metabolism, maintenance oxidative stress homeostasis, and epigenetic modifications. Furthermore, the dysregulation also impacts microenvironment immunity. can act as molecules that modulate immune function tolerance within reshaping anti-tumor response promoting evasion by cells. Moreover, influence behavior stromal cells, such cancer-associated fibroblasts, regulate ECM remodeling promote angiogenesis, thereby facilitating growth metastasis. Understanding intricate interplay between crucial significance. Expanding our knowledge multifaceted roles holds significant promise for development more effective therapies aimed at disrupting dependencies modulating enhance responses inhibit

Language: Английский

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Mutant p53 sustains serine-glycine synthesis and essential amino acids intake promoting breast cancer growth

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 25, 2023

Reprogramming of amino acid metabolism, sustained by oncogenic signaling, is crucial for cancer cell survival under nutrient limitation. Here we discovered that missense mutant p53 oncoproteins stimulate de novo serine/glycine synthesis and essential acids intake, promoting breast growth. Mechanistically, p53, unlike the wild-type counterpart, induces expression serine-synthesis-pathway enzymes L-type transporter 1 (LAT1)/CD98 heavy chain heterodimer. This effect exacerbated shortage, representing a p53-dependent metabolic adaptive response. When cells suffer scarcity, protein stabilized alterations an transcriptional program sustain proliferation. In patient-derived tumor organoids, pharmacological targeting either LAT1-mediated transport synergizes with shortage in blunting These findings reveal vulnerabilities potentially exploitable tackling tumors bearing TP53 mutations.

Language: Английский

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The (un)known crosstalk between metabolism and mechanotransduction: Implications for metabolic syndrome (MetS)-associated neurological complications

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 167678 - 167678

Published: Jan. 1, 2025

Metabolic syndrome (MetS) has been associated with disruptions in tissue mechanical homeostasis and inflammatory metabolic derangements. However, the direct correlation between alterations changes stiffness, whether they could play a role as upstream initiators of disease pathology remains to be investigated. This emerging concept yet put into clinical practice many questions concerning interplay extracellular matrix properties regulation pathways remain unsolved. review will highlight key foundational studies examining mutual cell metabolism mechanotransduction, opening lying ahead for better understanding MetS pathophysiology.

Language: Английский

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Mitochondria mechanosensing: The powerhouse fueling cellular force signaling

Current Biology, Journal Year: 2025, Volume and Issue: 35(2), P. R76 - R79

Published: Jan. 1, 2025

Language: Английский

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Mechanical forces in the tumor microenvironment: roles, pathways, and therapeutic approaches

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 12, 2025

Tumors often exhibit greater stiffness compared to normal tissues, primarily due increased deposition within the tumor stroma. Collagen, proteoglycans, laminin, and fibronectin are key components of extracellular matrix (ECM), interacting facilitate ECM assembly. Enhanced fiber density cross-linking result in elevated interstitial fluid pressure, subjecting tumors significant physical stress during growth. This mechanical is transduced intracellularly via integrins, Rho signaling pathway, Hippo thereby promoting invasion. Additionally, pressure fosters glycolysis cells, boosting energy production support metastasis. Mechanical cues also regulate macrophage polarization, maintaining an inflammatory microenvironment conducive survival. In summary, signals play a crucial role growth Understanding these their involvement progression essential for advancing our knowledge biology enhancing therapeutic approaches.

Language: Английский

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Mechanical cues rewire lipid metabolism and support chemoresistance in epithelial ovarian cancer cell lines OVCAR3 and SKOV3

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 22, 2025

Abstract Epithelial ovarian cancer (EOC) is one of the deadliest cancers in women, and acquired chemoresistance a major contributor aggressive phenotypes. Overcoming treatment failure disease recurrence therefore an ambitious goal. Ovarian develops biophysically challenging environment where cells are constantly exposed to mechanical deformation originating abdomen shear stress caused by accumulation ascitic fluid peritoneal cavity. Therefore, stimulation can be seen as inseparable part tumor microenvironment. The role biomechanics shaping metabolism emerging promises real game changer field biology. Focusing on two different epithelial cell lines (SKOV3 OVCAR3), we explored impact cellular behavior driven mechanosensitive transcription factors (TFs). Here, report data linking physical triggers alteration lipid metabolism, ultimately supporting increased chemoresistance. Mechanistically, induced adaptation membrane actin cytoskeleton which were accompanied regulation nuclear translocation SREBP2 YAP1. This was associated with cholesterol uptake/biosynthesis decreased sensitivity ruthenium-based anticancer drug BOLD-100. Overall, present study contributes shedding light molecular pathways connecting cues, responsiveness.

Language: Английский

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Mechanical force-mediated interactions between cancer cells and fibroblasts and their role in the progression of hepatocellular carcinoma

Journal of Cancer Metastasis and Treatment, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 22, 2024

Mechanical forces play a key role in the initiation and progression of cancer. Intercellular interactions between fibroblasts cancer cells contribute large portion mechanical tumor tissue. Hence, further investigation force-mediated intercellular is urgently needed, given slow progress management various solid cancers. In our previous study, we observed obvious hepatocellular carcinoma (HCC) through integrins ECM proteins by using coculture model discovered that these important roles 3D structure formation growth, suggesting their potential application HCC treatment. this review, summarize recent research field hopes providing insight into development anticancer strategies, with special focus on HCC.

Language: Английский

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Mechano‐induced arachidonic acid metabolism promotes keratinocyte proliferation through cPLA2 activity regulation

The FASEB Journal, Journal Year: 2024, Volume and Issue: 38(23)

Published: Dec. 5, 2024

Abstract Mechano‐induced keratinocyte hyperproliferation is reported to be associated with various skin diseases. Enhanced cell proliferation often requires the active metabolism of nutrients produce energy. However, how keratinocytes adapt their cellular homeostasis mechanical cues remains unclear. Here, we first found that stretched showed accumulation metabolic arachidonic acid by metabolomic analysis. Second, stretch promoted through activation cytosolic calcium‐dependent phospholipase A2 (cPLA2). Knockdown or inhibition cPLA2 could reduce release and inhibit in vitro vivo. Third, analyzing overlapping transcriptomes acid‐stimulated keratinocytes, identified upregulation hexokinase domain‐containing protein 1 (HKDC1) expression, a novel gene involved glucose metabolism, which was acid‐induced during stretching. Our data reveal regulation mechanism induces proliferation, thereby coupling mechanics microenvironment. Strategies change process may lead new way treat diseases are related biophysical forces.

Language: Английский

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Cellular dynamics as a marker of normal-to-cancer transition in human cells

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Nov. 29, 2023

Normal-to-cancer (NTC) transition is known to be closely associated cell´s biomechanical properties which are dependent on the dynamics of intracellular medium. This study probes different human cancer cells (breast, prostate and lung), concomitantly their healthy counterparts, aiming at characterising dynamical profile water in distinct cellular locations, for each type cell, how it changes between normal states. An increased plasticity cytomatrix observed upon normal-to-malignant transformation, lung carcinoma displaying highest flexibility followed by breast cancers. Also, show a behaviour relative prostate, with higher influence from hydration motions localised fast rotations NTC transformation. Quasielastic neutron scattering techniques allowed accurately distinguish processes taking place within these highly heterogeneous systems. The results thus obtained suggest that may regarded as specific reporter conditions-either or malignant.

Language: Английский

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