MiR-769-5p of macrophage exosomes induced by GRP78 promotes stemness and chemoresistance in colorectal cancer DOI Creative Commons
Jinmiao Tian, Lichao Zhang, Xiaoqin La

и другие.

Cell Death and Disease, Год журнала: 2025, Номер 16(1)

Опубликована: Март 5, 2025

The tumor microenvironment (TME) plays an important role in tumorigenesis and development. Tumor-associated macrophages (TAMs) are essential members of the TME, exosomes miRNAs they secrete crucial regulation. Our previous study showed that GRP78-induced infinitely tend to be M2-type TAMs. In this study, M0 macrophage were collected co-incubated with colorectal cancer (CRC) cells. results implied induced by GRP78 (GRP78-exos) significantly promoted stemness chemoresistance CRC vitro vivo. Further, top 5 upregulated GRP78-exos obtained from miRNA sequencing data. qRT-PCR validation revealed miR-769-5p was most observably could directly transferred into cells via GRP78-exos. Mechanistically, indicated targeted MAPK1 regulate cell cycle-related proteins RB1, cyclin D1, E1. This contributes entering a quiescent state, which leads development chemoresistance. Moreover, is also expressed higher tissues 5-FU-resistant patients. summary, findings indicate novel function as potential marker for diagnosis treatment chemotherapy resistance CRC.

Язык: Английский

Cancer stem cells: advances in knowledge and implications for cancer therapy DOI Creative Commons

Xianjing Chu,

Wentao Tian,

Jiaoyang Ning

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Июль 5, 2024

Abstract Cancer stem cells (CSCs), a small subset of in tumors that are characterized by self-renewal and continuous proliferation, lead to tumorigenesis, metastasis, maintain tumor heterogeneity. continues be significant global disease burden. In the past, surgery, radiotherapy, chemotherapy were main cancer treatments. The technology treatments develop advance, emergence targeted therapy, immunotherapy provides more options for patients certain extent. However, limitations efficacy treatment resistance still inevitable. Our review begins with brief introduction historical discoveries, original hypotheses, pathways regulate CSCs, such as WNT/β-Catenin, hedgehog, Notch, NF-κB, JAK/STAT, TGF-β, PI3K/AKT, PPAR pathway, their crosstalk. We focus on role CSCs various therapeutic outcomes resistance, including how affect content alteration related molecules, CSCs-mediated clinical value targeting refractory, progressed or advanced tumors. summary, efficacy, method is difficult determine. Clarifying regulatory mechanisms biomarkers currently mainstream idea.

Язык: Английский

Процитировано

110

TXNIP: A Double-Edged Sword in Disease and Therapeutic Outlook DOI Creative Commons
Min Pan, Fengping Zhang, Kai Qu

и другие.

Oxidative Medicine and Cellular Longevity, Год журнала: 2022, Номер 2022, С. 1 - 14

Опубликована: Апрель 11, 2022

Thioredoxin-interacting protein (TXNIP) was originally named vitamin D3 upregulated protein-1 (VDUP1) because of its ability to bind thioredoxin (TRX) and inhibit TRX function expression. TXNIP is an alpha-arrestin that essential for redox homeostasis in the human body. may act as a double-edged sword cell. The balance crucial. A study has shown can travel between diverse intracellular locations different proteins play roles under oxidative stress. primary induce apoptosis or pyroptosis also inhibits proliferation migration cancer cells, although levels decrease, diminishes various cancers. In this review, we summarized main structure, binding proteins, pathways, role diseases, aiming explore TXNIP, expect it be helpful future treatment using therapeutic target.

Язык: Английский

Процитировано

73

Immunosuppressive tumor microenvironment in the progression, metastasis, and therapy of hepatocellular carcinoma: from bench to bedside DOI Creative Commons
Yue Yin,

Weibo Feng,

Jie Chen

и другие.

Experimental Hematology and Oncology, Год журнала: 2024, Номер 13(1)

Опубликована: Авг. 1, 2024

Abstract Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with high incidence, recurrence, and metastasis rates. The emergence of immunotherapy has improved the treatment advanced HCC, but problems such as drug resistance immune-related adverse events still exist in clinical practice. immunosuppressive tumor microenvironment (TME) HCC restricts efficacy essential for progression metastasis. Therefore, it necessary to elucidate mechanisms behind TME develop apply immunotherapy. This review systematically summarizes pathogenesis formation TME, by which accelerates We also status further discuss existing challenges potential therapeutic strategies targeting TME. hope inspire optimizing innovating immunotherapeutic comprehensively understanding structure function HCC.

Язык: Английский

Процитировано

30

Crosstalk between extracellular vesicles and tumor-associated macrophage in the tumor microenvironment DOI
Qiao Yi Chen, Beibei Gao,

Dongdong Tong

и другие.

Cancer Letters, Год журнала: 2022, Номер 552, С. 215979 - 215979

Опубликована: Окт. 26, 2022

Язык: Английский

Процитировано

41

The role of TXNIP in cancer: a fine balance between redox, metabolic, and immunological tumor control DOI Creative Commons
Jinhai Deng, Teng Pan, Zaoqu Liu

и другие.

British Journal of Cancer, Год журнала: 2023, Номер 129(12), С. 1877 - 1892

Опубликована: Окт. 4, 2023

Abstract Thioredoxin-interacting protein (TXNIP) is commonly considered a master regulator of cellular oxidation, regulating the expression and function Thioredoxin (Trx). Recent work has identified that TXNIP far wider range additional roles: from glucose lipid metabolism, to cell cycle arrest inflammation. Its increased by stressors found in neoplastic cells tumor microenvironment (TME), and, as such, been extensively studied cancers. In this review, we evaluate current literature regarding regulation TXNIP, highlighting its emerging role modulating signaling between different types within TME. We then assess future translational opportunities associated challenges area. An improved understanding functions mechanisms cancers may enhance suitability therapeutic target.

Язык: Английский

Процитировано

28

Biological impact and therapeutic implication of tumor-associated macrophages in hepatocellular carcinoma DOI Creative Commons
Deming Li, Ting Zhang, Ye Guo

и другие.

Cell Death and Disease, Год журнала: 2024, Номер 15(7)

Опубликована: Июль 12, 2024

The tumor microenvironment is a complex space comprised of normal, cancer and immune cells. macrophages are considered as the most abundant cells in their function tumorigenesis interesting. Macrophages can be present M1 M2 polarization that show anti-cancer oncogenic activities, respectively. Tumor-associated (TAMs) mainly have they increase due to secretion factors, cytokines affecting molecular pathways. Hepatocellular carcinoma (HCC) among predominant tumors liver spite understanding its pathogenesis, role progression still requires more attention. presence TAMs HCC causes an growth invasion one reasons induction glycolysis such metabolic reprogramming makes distinct from normal promotes malignancy. Since stimulates HCC, networks regulating conversion been highlighted moreover, drugs compounds with ability targeting suppressing phenotypes or at least activity utilized. aggressive behavior biological functions result development therapy resistance. provide cell-cell communication by secreting exosomes having various types biomolecules transfer change activity. Finally, non-coding RNA transcripts affect HCC.

Язык: Английский

Процитировано

14

The Cancer Antioxidant Regulation System in Therapeutic Resistance DOI Creative Commons

Xuanhao Gu,

Chunyang Mu,

Rujia Zheng

и другие.

Antioxidants, Год журнала: 2024, Номер 13(7), С. 778 - 778

Опубликована: Июнь 27, 2024

Antioxidants play a pivotal role in neutralizing reactive oxygen species (ROS), which are known to induce oxidative stress. In the context of cancer development, cells adeptly maintain elevated levels both ROS and antioxidants through process termed "redox reprogramming". This balance optimizes proliferative influence while simultaneously reducing potential for cause damage cell. some cases, adapted antioxidant machinery can hamper efficacy treatments neoplastic diseases, representing significant facet resistance mechanisms observed therapy. this review, we outline contribution systems therapeutic resistance. We detail fundamental constituents these systems, encompassing central regulatory involving transcription factors (of particular importance is KEAP1/NRF2 signaling axis), molecular effectors antioxidants, auxiliary responsible NADPH generation. Furthermore, present recent clinical trials based on targeted treatment cancer, assessing as well challenges strategy Additionally, summarize pressing issues field, with aim illuminating path toward emergence novel anticancer approaches by orchestrating redox signaling.

Язык: Английский

Процитировано

12

Mutual regulation of PD-L1 immunosuppression between tumor-associated macrophages and tumor cells: a critical role for exosomes DOI Creative Commons

Banglu Wang,

Daoan Cheng,

Danyu Ma

и другие.

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Янв. 9, 2024

Abstract Tumor cells primarily employ the PD-1/PD-L1 pathway to thwart anti-tumor capabilities of T lymphocytes, inducing immunosuppression. This occurs through direct interaction PD-L1 with PD-1 on lymphocyte surfaces. Recent research focusing tumor microenvironment has illuminated pivotal role immune cells, particularly tumor-associated macrophages (TAMs), in facilitating PD-L1-mediated Exosomes, characterized by their ability convey information and be engulfed significantly contribute promoting TAM involvement establishing immunosuppression within microenvironment. In addition receiving signals from tumor-derived exosomes that promote expression, TAMs also exert control over expression release exosomes. paper aims summarize mechanisms which participate this process, identify crucial factors influence these mechanisms, explore innovative strategies for inhibiting or reversing tumor-promoting effects targeting

Язык: Английский

Процитировано

11

Exosome crosstalk between cancer stem cells and tumor microenvironment: cancer progression and therapeutic strategies DOI Creative Commons
Qi Li, Guangpeng He, Yifan Yu

и другие.

Stem Cell Research & Therapy, Год журнала: 2024, Номер 15(1)

Опубликована: Ноя. 22, 2024

Abstract Cancer stem cells (CSCs) represent a small yet pivotal subset of tumor endowed with self-renewal capabilities. These are intricately linked to progression and central drug resistance, metastasis, recurrence. The microenvironment (TME) encompasses the cancer their surrounding milieu, including immune inflammatory cells, cancer-associated fibroblasts, adjacent stromal tissues, vasculature, variety cytokines chemokines. Within TME, such as endothelial adipocytes, fibroblasts release growth factors, cytokines, chemokines, exosomes, which can either sustain or disrupt CSCs, thereby influencing progression. Conversely, CSCs also secrete affecting various components TME. Exosomes, extracellular vesicles (EVs), carry complex cargo nucleic acids, proteins, lipids, playing crucial role in communication between This review primarily focuses on impact exosomes secreted by (CSC-exo) progression, roles maintaining stemness, promoting angiogenesis, facilitating inducing suppression, contributing resistance. Additionally, we discuss how different within TME affect CSCs. Finally, explore potential utilizing mitigate detrimental effects target eliminate them. A thorough understanding exosome-mediated crosstalk could provide valuable insights for developing targeted therapies against

Язык: Английский

Процитировано

11

Degenerated nucleus pulposus cells derived exosome carrying miR-27a-3p aggravates intervertebral disc degeneration by inducing M1 polarization of macrophages DOI Creative Commons
Xin Zhao, Zhen Sun,

Benchi Xu

и другие.

Journal of Nanobiotechnology, Год журнала: 2023, Номер 21(1)

Опубликована: Сен. 4, 2023

Intervertebral disc degeneration (IVDD) is a major contributor to spinal disorders. Previous studies have indicated that the infiltration of immunocytes, specifically macrophages, plays crucial role in advancement IVDD. Exosomes (exo) are believed play significant intercellular communication. This study aims investigate exosomes derived from degenerated nucleus pulposus (dNPc) process macrophages M1 polarization.Nucleus (NP) tissue and cells (NPc) were collected patients with intervertebral idiopathic scoliosis. Immunohistochemistry analysis was performed determine number NP tissue. Subsequently, (dNPc-exo) non-degenerated (nNPc-exo) co-cultured M0 which induced THP-1 cells. The phenotype assessed using western blot, flow cytometry, immunofluorescence staining, qRT-PCR. RNA-sequencing conducted examine expression levels microRNAs dNPc-exo nNPc-exo groups, qRT-PCR effect pf different microRNA induce macrophage polarization. Furthermore, blot employed demonstrate regulatory carried by on downstream target signaling pathways macrophages. Finally, an animal model IVDD utilized impact inducing polarization its process.In this study, we observed increase as (IVD) degraded. Additionally, discovered dNPc releases could promote towards phenotype. Notably, through identified miR-27a-3p highly expressed miRNA group, significantly influences induction And then, has ability transport PPARγ/NFκB/PI3K/AKT pathway, thereby influencing We experiments rat carrying actually exacerbated degradation IVD.In conclusion, our findings highlight provide basis for further investigation into mechanism potential exosome-based therapy.

Язык: Английский

Процитировано

21