scholarly journals Vimentin filaments drive migratory persistence in polyploidal cancer cells

2020 ◽  
Vol 117 (43) ◽  
pp. 26756-26765
Author(s):  
Botai Xuan ◽  
Deepraj Ghosh ◽  
Joy Jiang ◽  
Rachelle Shao ◽  
Michelle R. Dawson
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Structural Integrity ◽  
Single Cell Analysis ◽  
Critical Role ◽  
Critical Function ◽  
Rna Knockdown ◽  
Interfering Rna ◽  
The Impact

Polyploidal giant cancer cells (PGCCs) are multinucleated chemoresistant cancer cells found in heterogeneous solid tumors. Due in part to their apparent dormancy, the effect of PGCCs on cancer progression has remained largely unstudied. Recent studies have highlighted the critical role of PGCCs as aggressive and chemoresistant cancer cells, as well as their ability to undergo amitotic budding to escape dormancy. Our recent study demonstrated the unique biophysical properties of PGCCs, as well as their unusual migratory persistence. Here we unveil the critical function of vimentin intermediate filaments (VIFs) in maintaining the structural integrity of PGCCs and enhancing their migratory persistence. We performed in-depth single-cell analysis to examine the distribution of VIFs and their role in migratory persistence. We found that PGCCs rely heavily on their uniquely distributed and polarized VIF network to enhance their transition from a jammed to an unjammed state to allow for directional migration. Both the inhibition of VIFs with acrylamide and small interfering RNA knockdown of vimentin significantly decreased PGCC migration and resulted in a loss of PGCC volume. Because PGCCs rely on their VIF network to direct migration and to maintain their enlarged morphology, targeting vimentin or vimentin cross-linking proteins could provide a therapeutic approach to mitigate the impact of these chemoresistant cells in cancer progression and to improve patient outcomes with chemotherapy.

scholarly journals Paracrine interactions between epithelial cells promote colon cancer growth

2020 ◽  
Author(s):  
Guillaume Jacquemin ◽  
Annabelle Wurmser ◽  
Mathilde Huyghe ◽  
Wenjie Sun ◽  
Meghan Perkins ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cancer Cells ◽  
Stromal Cells ◽  
Critical Role ◽  
Essential Factor ◽  
Transcriptional Responses ◽  
Tumour Formation ◽  
Different Types ◽  
The Impact

AbstractTumours are complex ecosystems composed of different types of cells that communicate and influence each other. While the critical role of stromal cells in affecting tumour growth is well established, the impact of mutant cancer cells on healthy surrounding tissues remains poorly defined. Here, we uncovered a paracrine mechanism by which intestinal cancer cells reactivate foetal and regenerative Yap-associated transcriptional programs in neighbouring wildtype epithelial cells, rendering them adapted to thrive in the tumour context. We identified the glycoprotein Thrombospondin-1 (Thbs1) as the essential factor that mediates non-cell autonomous morphological and transcriptional responses. Importantly, Thbs1 is associated with bad prognosis in several human cancers. This study reveals the Thbs1-YAP axis as the mechanistic link mediating paracrine interactions between epithelial cells, promoting tumour formation and progression.

scholarly journals Leupaxin Promotes Bladder Cancer Proliferation, Metastasis, and Angiogenesis Through the PI3K/AKT Pathway

2018 ◽  
Vol 47 (6) ◽  
pp. 2250-2260 ◽  
Author(s):  
Teng Hou ◽  
Lijie Zhou ◽  
Longwang Wang ◽  
Gallina Kazobinka ◽  
Yumao Chen ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Akt Pathway ◽  
Advanced Tumor Stage ◽  
Large Tumor ◽  
Advanced Tumor ◽  
Bladder Cancer Cells ◽  
The Impact

Background/Aims: Leupaxin (LPXN) is a member of the paxillin protein family. Several studies have reported that LPXN regulates cancer development; however, the role of LPXN in bladder cancer remains unknown. Methods: The expression of LPXN in bladder cancer cells and tissues was determined by real-time PCR, western blotting, and immunohistochemistry, respectively. The biological role of LPXN in bladder cancer cell proliferation, invasion, and angiogenesis was explored both in vitro and in vivo. Results: LPXN expression was elevated in bladder cancer tissues and cell lines compared to adjacent non-tumor tissues and normal urothelial cells. High LPXN expression was correlated with large tumor size, advanced tumor stage, and poor survival in bladder cancer patients. Overexpression of LPXN significantly promoted the proliferation, invasion, and angiogenesis of bladder cancer cells, while suppressing LPXN had the opposite effects. The impact on tumor progression was abolished by inhibiting PI3K/ AKT signaling pathway. We further demonstrated that LPXN probably up-regulated S100P via the PI3K/AKT pathway. Conclusions: LPXN may facilitate bladder cancer progression by upregulating the expression of S100P via PI3K/AKT pathway. These results provide a novel insight into the role of LPXN in tumorigenesis and progression of bladder cancer and potential therapeutic target of bladder cancer.

scholarly journals The Role of miRNAs as Key Regulators in the Neoplastic Microenvironment

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
K. K. Wentz-Hunter ◽  
J. A. Potashkin
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Posttranscriptional Regulation ◽  
Noncoding Rna ◽  
Critical Role ◽  
Large Body ◽  
Small Noncoding Rna ◽  
Clinical Patient

The neoplastic microenvironment has been recognized to play a critical role in the development of cancer. Although a large body of evidence has established the importance of the cancer microenvironment, the manners of crosstalk between it and the cancer cells still remains unclear. Emerging mechanisms of communication include microRNAs (miRNAs). miRNAs are small noncoding RNA molecules that are involved in the posttranscriptional regulation of mRNA. Both intracellular and circulating miRNAs are differentially expressed in cancer and some of these alterations have been correlated with clinical patient outcomes. The role of miRNAs in the tumor microenvironment has only recently become a focus of research, however. In this paper, we discuss the influence of miRNAs on the tumor microenvironment as it relates to cancer progression. We conclude that miRNAs are a critical component in understanding invasion and metastasis of cancer cells.

scholarly journals NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2999
Author(s):  
Deborah Reynaud ◽  
Roland Abi Nahed ◽  
Nicolas Lemaitre ◽  
Pierre-Adrien Bolze ◽  
Wael Traboulsi ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Cells ◽  
Major Gene ◽  
Critical Role ◽  
Orthotopic Model ◽  
Independent Manner ◽  
Maternal Immune Response ◽  
The Impact

The inflammatory gene NLRP7 is the major gene responsible for recurrent complete hydatidiform moles (CHM), an abnormal pregnancy that can develop into gestational choriocarcinoma (CC). However, the role of NLRP7 in the development and immune tolerance of CC has not been investigated. Three approaches were employed to define the role of NLRP7 in CC development: (i) a clinical study that analyzed human placenta and sera collected from women with normal pregnancies, CHM or CC; (ii) an in vitro study that investigated the impact of NLRP7 knockdown on tumor growth and organization; and (iii) an in vivo study that used two CC mouse models, including an orthotopic model. NLRP7 and circulating inflammatory cytokines were upregulated in tumor cells and in CHM and CC. In tumor cells, NLRP7 functions in an inflammasome-independent manner and promoted their proliferation and 3D organization. Gravid mice placentas injected with CC cells invalidated for NLRP7, exhibited higher maternal immune response, developed smaller tumors, and displayed less metastases. Our data characterized the critical role of NLRP7 in CC and provided evidence of its contribution to the development of an immunosuppressive maternal microenvironment that not only downregulates the maternal immune response but also fosters the growth and progression of CC.

scholarly journals A non-toxic, reversibly released imaging probe for oral cancer that is derived from natural compounds

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Magda Ghanim ◽  
Nicola Relitti ◽  
Gavin McManus ◽  
Stefania Butini ◽  
Andrea Cappelli ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Cancer Progression ◽  
Intraoperative Imaging ◽  
Critical Role ◽  
Water Soluble ◽  
Stem Cell Marker ◽  
Squamous Cells ◽  
Tissue Identification ◽  
Tumorigenic Potential ◽  
The Impact

AbstractCD44 is emerging as an important receptor biomarker for various cancers. Amongst these is oral cancer, where surgical resection remains an essential mode of treatment. Unfortunately, surgery is frequently associated with permanent disfigurement, malnutrition, and functional comorbidities due to the difficultly of tumour removal. Optical imaging agents that can guide tumour tissue identification represent an attractive approach to minimising the impact of surgery. Here, we report the synthesis of a water-soluble fluorescent probe, namely HA-FA-HEG-OE (compound 1), that comprises components originating from natural sources: oleic acid, ferulic acid and hyaluronic acid. Compound 1 was found to be non-toxic, displayed aggregation induced emission and accumulated intracellularly in vesicles in SCC-9 oral squamous cells. The uptake of 1 was fully reversible over time. Internalization of compound 1 occurs through receptor mediated endocytosis; uniquely mediated through the CD44 receptor. Uptake is related to tumorigenic potential, with non-tumorigenic, dysplastic DOK cells and poorly tumorigenic MCF-7 cells showing only low intracellular levels and highlighting the critical role of endocytosis in cancer progression and metastasis. Together, the recognised importance of CD44 as a cancer stem cell marker in oral cancer, and the reversible, non-toxic nature of 1, makes it a promising agent for real time intraoperative imaging.

scholarly journals The metabolic adaptation mechanism of metastatic organotropism

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Chao Wang ◽  
Daya Luo
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Cancer Metabolism ◽  
Cancer Metastasis ◽  
Tumour Microenvironment ◽  
Metabolic Adaptation ◽  
Adaptation Mechanism ◽  
Metastatic Sites ◽  
The Impact

AbstractMetastasis is a complex multistep cascade of cancer cell extravasation and invasion, in which metabolism plays an important role. Recently, a metabolic adaptation mechanism of cancer metastasis has been proposed as an emerging model of the interaction between cancer cells and the host microenvironment, revealing a deep and extensive relationship between cancer metabolism and cancer metastasis. However, research on how the host microenvironment affects cancer metabolism is mostly limited to the impact of the local tumour microenvironment at the primary site. There are few studies on how differences between the primary and secondary microenvironments promote metabolic changes during cancer progression or how secondary microenvironments affect cancer cell metastasis preference. Hence, we discuss how cancer cells adapt to and colonize in the metabolic microenvironments of different metastatic sites to establish a metastatic organotropism phenotype. The mechanism is expected to accelerate the research of cancer metabolism in the secondary microenvironment, and provides theoretical support for the generation of innovative therapeutic targets for clinical metastatic diseases.

scholarly journals Microbiota Alterations in Precancerous Colon Lesions: A Systematic Review

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3061
Author(s):  
Francesca Aprile ◽  
Giovanni Bruno ◽  
Rossella Palma ◽  
Maria Teresa Mascellino ◽  
Cristina Panetta ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Endoscopic Resection ◽  
Causative Role ◽  
Health It ◽  
Microbial Dysbiosis ◽  
Pubmed Database ◽  
The Impact ◽  
The Relationship ◽  
Preventive Role

Gut microbiota plays an important role in human health. It may promote carcinogenesis and is related to several diseases of the gastrointestinal tract. This study of microbial dysbiosis in the etiology of colorectal adenoma aimed to investigate the possible causative role of microbiota in the adenoma–carcinoma sequence and its possible preventive role. A systematic, PRISMA-guided review was performed. The PubMed database was searched using “adenoma microbiota” and selecting original articles between January 2010 and May 2020 independently screened. A higher prevalence of Proteobacteria, Fusobacteria, and Bacteroidetes phyla was observed in the fecal luminal and mucosa-associated microbiota of patients with adenoma. However, other studies provided evidence of depletion of Clostridium, Faecalibacterium, Bacteroides and Romboutsia. Results on the relationship between adenoma endoscopic resection and microbiota were inconsistent. In conclusion, none of the analyzed studies developed a predictive model that could differentiate adenoma from non-adenoma patients, and therefore, to prevent cancer progression. The impact of adenoma’s endoscopic resection on microbiota was investigated, but the results were inconclusive. Further research in the field is required.

scholarly journals Specialized Pro-Resolving Lipid Mediators in Neonatal Cardiovascular Physiology and Diseases

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 933
Author(s):  
Andrea Gila-Diaz ◽  
Gloria Herranz Carrillo ◽  
Pratibha Singh ◽  
David Ramiro-Cortijo
Keyword(s):  
Tissue Repair ◽  
Cardiovascular Health ◽  
Critical Role ◽  
Potential Effect ◽  
Lipid Mediators ◽  
Physiological Effects ◽  
Therapeutic Approaches ◽  
The Impact ◽  
Long Chain

Cardiovascular disease remains a leading cause of mortality worldwide. Unresolved inflammation plays a critical role in cardiovascular diseases development. Specialized Pro-Resolving Mediators (SPMs), derived from long chain polyunsaturated fatty acids (LCPUFAs), enhances the host defense, by resolving the inflammation and tissue repair. In addition, SPMs also have anti-inflammatory properties. These physiological effects depend on the availability of LCPUFAs precursors and cellular metabolic balance. Most of the studies have focused on the impact of SPMs in adult cardiovascular health and diseases. In this review, we discuss LCPUFAs metabolism, SPMs, and their potential effect on cardiovascular health and diseases primarily focusing in neonates. A better understanding of the role of these SPMs in cardiovascular health and diseases in neonates could lead to the development of novel therapeutic approaches in cardiovascular dysfunction.

Cationicity and hydrophobicity enhance the cytotoxic potency of Phoratoxin C anticancer peptide analogues against triple negative breast cancer cells

2021 ◽  
Vol 17 ◽  
Author(s):  
Chu Xin Ng ◽  
Cheng Foh Le ◽  
Sau Har Lee
Keyword(s):  
Cancer Cells ◽  
Anticancer Agents ◽  
Breast Cancer Cells ◽  
Critical Role ◽  
Three Dimensional ◽  
Vero Cells ◽  
Anticancer Peptides ◽  
Α Helix ◽  
Peptide Analogues

Background: Anticancer peptides (ACPs) have received increasing attention as a promising class of novel anticancer agents owing to its potent and rapid cytotoxic properties. In this study, we aim to investigate the effects of cationicity and hydrophobicity in modulating the cytotoxicity of PtxC, a class of ACP from the leafy mistletoe Phoradendron tomentosum against the MDA-MB-231 and Vero cells. Method: We designed a series of four PtxC analogues (PA1 – PA4) by residual substitutions with specific amino acids to introduce the specific charge and hydrophobicity alterations to the analogues. The cytotoxicity strength of the PtxC analogues on MDA-MB-231 and Vero cells were tested by using MTT assay at 24 hours post treatment. Results: PA1, PA2 and PA4 displayed marked increases in cytotoxicity against both MDA-MB-231 and Vero cells and can be ranked in the order of PA2 > PA4 > PA1 > PtxC > PA3. Sequence-activity relationship analyses of the designed analogues showed that an increase in the level of cationicity and hydrophobicity correlated well with the enhanced cytotoxic activity of PtxC analogues. This was observed with PA1 (netC +8) and PA2 (netC +10) in comparison to PtxC (netC +7). Similar finding was observed for PA4 (GRAVY +0.070) in contrast to PtxC (GRAVY -0.339). Three-dimensional modelling predicted a double α-helix structure in PtxC class of ACP. The larger first helix in PA2 and PA4 was suggested to be responsible for the enhanced cytotoxicity observed. Conclusion: The critical role of cationicity and hydrophobicity in enhancing cytotoxicity of PtxC class of ACPs were clearly demonstrated in our study. The current findings could be extrapolated to benefit peptide design strategy in other classes of ACPs toward the discovery of highly potent ACPs against cancer cells as potential novel therapeutic agents.

scholarly journals A Dual Role of Heme Oxygenase-1 in Cancer Cells

2018 ◽  
Vol 20 (1) ◽  
pp. 39 ◽  
Author(s):  
Shih-Kai Chiang ◽  
Shuen-Ei Chen ◽  
Ling-Chu Chang
Keyword(s):  
Cell Death ◽  
Heme Oxygenase ◽  
Cancer Progression ◽  
Critical Role ◽  
Causative Factor ◽  
Protective Role ◽  
Dark Side ◽  
Heme Oxygenase 1 ◽  
Cellular Iron

Heme oxygenase (HO)-1 is known to metabolize heme into biliverdin/bilirubin, carbon monoxide, and ferrous iron, and it has been suggested to demonstrate cytoprotective effects against various stress-related conditions. HO-1 is commonly regarded as a survival molecule, exerting an important role in cancer progression and its inhibition is considered beneficial in a number of cancers. However, increasing studies have shown a dark side of HO-1, in which HO-1 acts as a critical mediator in ferroptosis induction and plays a causative factor for the progression of several diseases. Ferroptosis is a newly identified iron- and lipid peroxidation-dependent cell death. The critical role of HO-1 in heme metabolism makes it an important candidate to mediate protective or detrimental effects via ferroptosis induction. This review summarizes the current understanding on the regulatory mechanisms of HO-1 in ferroptosis. The amount of cellular iron and reactive oxygen species (ROS) is the determinative momentum for the role of HO-1, in which excessive cellular iron and ROS tend to enforce HO-1 from a protective role to a perpetrator. Despite the dark side that is related to cell death, there is a prospective application of HO-1 to mediate ferroptosis for cancer therapy as a chemotherapeutic strategy against tumors.

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