scholarly journals Towards a Better Understanding of the Relationships between Galectin-7, p53 and MMP-9 during Cancer Progression

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 879
Author(s):  
Yves St-Pierre
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
New Paradigm ◽  
Cancer Subtypes ◽  
Functional Relationships ◽  
Invasive Behavior ◽  
Cancer Field ◽  
The Matrix ◽  
Cancer Types

It has been almost 25 years since the discovery of galectin-7. This member of the galectin family has attracted interest from many working in the cancer field given its highly restricted expression profile in epithelial cells and the fact that cancers of epithelial origin (carcinoma) are among the most frequent and deadly cancer subtypes. Initially described as a p53-induced gene and associated with apoptosis, galectin-7 is now recognized as having a protumorigenic role in many cancer types. Several studies have indeed shown that galectin-7 is associated with aggressive behavior of cancer cells and induces expression of MMP-9, a member of the matrix metalloproteinases (MMP) family known to confer invasive behavior to cancer cells. It is therefore not surprising that many studies have examined its relationships with p53 and MMP-9. However, the relationships between galectin-7 and p53 and MMP-9 are not always clear. This is largely because p53 is often mutated in cancer cells and such mutations drastically change its functions and, consequently, its association with galectin-7. In this review, we discuss the functional relationships between galectin-7, p53 and MMP-9 and reconcile some apparently contradictory observations. A better understanding of these relationships will help to develop a working hypothesis and model that will provide the basis for further research in the hope of establishing a new paradigm for tackling the role of galectin-7 in cancer.

scholarly journals Meiosis and Kinetochore genes are used by cancer cells as genome destabilizers and transformation catalysts

2019 ◽  
Author(s):  
Roshina Thapa ◽  
Swetha Vasudevan ◽  
Mimi Abo-Ayoub Ashqar ◽  
Eli Reich ◽  
Nataly Kravchenko-Balasha ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Genome Instability ◽  
Chromosome Instability ◽  
Information Theoretic ◽  
Cancer Types ◽  
Altered Gene ◽  
The Relationship ◽  
Hct116 Cells

AbstractCancer cells have an altered transcriptome which contributes to their altered behaviors compared to normal cells. Indeed, many tumors express high levels of genes participating in meiosis or kinetochore biology, but the role of this high expression has not been fully elucidated. In this study we explore the relationship between this overexpression and genome instability and transformation capabilities of cancer cells. For this, we obtained expression data from 5 different cancer types which were analyzed using computational information-theoretic analysis. We were able to show that highly expressed meiotic/kinetochore genes were enriched in the altered gene expression subnetworks characterizing unstable cancer types with high chromosome instability (CIN). However, altered subnetworks found in the cancers with low CIN did not include meiotic and kinetochore genes. Representative gene candidates, found by the analysis to be correlated with a CIN phenotype, were further explored by transfecting genomically-stable (HCT116) and unstable (MCF7) cancer cell lines with vectors overexpressing those genes. This overexpression resulted in an increase in the numbers of abnormal cell divisions and defective spindle formations and in increased transformation properties in stable cancer HCT116 cells. Interestingly, the same properties were less affected by the overexpressed genes in the unstable MCF7 cancer cells. Our results indicate that overexpression of both meiosis and kinetochore genes is capable of driving genomic instability and cancer progression.

scholarly journals miR-205 in Breast Cancer: State of the Art

2020 ◽  
Vol 22 (1) ◽  
pp. 27
Author(s):  
Ilaria Plantamura ◽  
Alessandra Cataldo ◽  
Giulia Cosentino ◽  
Marilena V. Iorio
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Normal Breast ◽  
Response To Therapy ◽  
Aberrant Expression ◽  
Open Questions ◽  
Tumor Tissues ◽  
Breast Physiology ◽  
Cancer Types

Despite its controversial roles in different cancer types, miR-205 has been mainly described as an oncosuppressive microRNA (miRNA), with some contrasting results, in breast cancer. The role of miR-205 in the occurrence or progression of breast cancer has been extensively studied since the first evidence of its aberrant expression in tumor tissues versus normal counterparts. To date, it is known that the expression of miR-205 in the different subtypes of breast cancer is decreasing from the less aggressive subtype, estrogen receptor/progesterone receptor positive breast cancer, to the more aggressive, triple negative breast cancer, influencing metastasis capability, response to therapy and patient survival. In this review, we summarize the most important discoveries that have highlighted the functional role of this miRNA in breast cancer initiation and progression, in stemness maintenance, in the tumor microenvironment, its potential role as a biomarker and its relevance in normal breast physiology—the still open questions. Finally, emerging evidence reveals the role of some lncRNAs in breast cancer progression as sponges of miR-205. Here, we also reviewed the studies in this field.

scholarly journals Role of the NUDT Enzymes in Breast Cancer

2021 ◽  
Vol 22 (5) ◽  
pp. 2267
Author(s):  
Roni H. G. Wright ◽  
Miguel Beato
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Breast Cancers ◽  
Metastatic Colonization ◽  
Hormone Receptor Positive ◽  
Aggressive Cancer ◽  
Cancer Types ◽  
Metastatic Process

Despite global research efforts, breast cancer remains the leading cause of cancer death in women worldwide. The majority of these deaths are due to metastasis occurring years after the initial treatment of the primary tumor and occurs at a higher frequency in hormone receptor-positive (Estrogen and Progesterone; HR+) breast cancers. We have previously described the role of NUDT5 (Nudix-linked to moiety X-5) in HR+ breast cancer progression, specifically with regards to the growth of breast cancer stem cells (BCSCs). BCSCs are known to be the initiators of epithelial-to-mesenchyme transition (EMT), metastatic colonization, and growth. Therefore, a greater understanding of the proteins and signaling pathways involved in the metastatic process may open the door for therapeutic opportunities. In this review, we discuss the role of NUDT5 and other members of the NUDT family of enzymes in breast and other cancer types. We highlight the use of global omics data based on our recent phosphoproteomic analysis of progestin signaling pathways in breast cancer cells and how this experimental approach provides insight into novel crosstalk mechanisms for stratification and drug discovery projects aiming to treat patients with aggressive cancer.

scholarly journals Characterizing Intercellular Communication of Pan-Cancer Reveals SPP1+ Tumor-Associated Macrophage Expanded in Hypoxia and Promoting Cancer Malignancy Through Single-Cell RNA-Seq Data

2021 ◽  
Vol 9 ◽  
Author(s):  
Jinfen Wei ◽  
Zixi Chen ◽  
Meiling Hu ◽  
Ziqing He ◽  
Dawei Jiang ◽  
...  
Keyword(s):  
Single Cell ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Single Cells ◽  
Matrix Remodeling ◽  
Rna Seq ◽  
Mesenchymal Transition ◽  
Tumor Associated Macrophage ◽  
Cancer Types

Hypoxia is a characteristic of tumor microenvironment (TME) and is a major contributor to tumor progression. Yet, subtype identification of tumor-associated non-malignant cells at single-cell resolution and how they influence cancer progression under hypoxia TME remain largely unexplored. Here, we used RNA-seq data of 424,194 single cells from 108 patients to identify the subtypes of cancer cells, stromal cells, and immune cells; to evaluate their hypoxia score; and also to uncover potential interaction signals between these cells in vivo across six cancer types. We identified SPP1+ tumor-associated macrophage (TAM) subpopulation potentially enhanced epithelial–mesenchymal transition (EMT) by interaction with cancer cells through paracrine pattern. We prioritized SPP1 as a TAM-secreted factor to act on cancer cells and found a significant enhanced migration phenotype and invasion ability in A549 lung cancer cells induced by recombinant protein SPP1. Besides, prognostic analysis indicated that a higher expression of SPP1 was found to be related to worse clinical outcome in six cancer types. SPP1 expression was higher in hypoxia-high macrophages based on single-cell data, which was further validated by an in vitro experiment that SPP1 was upregulated in macrophages under hypoxia-cultured compared with normoxic conditions. Additionally, a differential analysis demonstrated that hypoxia potentially influences extracellular matrix remodeling, glycolysis, and interleukin-10 signal activation in various cancer types. Our work illuminates the clearer underlying mechanism in the intricate interaction between different cell subtypes within hypoxia TME and proposes the guidelines for the development of therapeutic targets specifically for patients with high proportion of SPP1+ TAMs in hypoxic lesions.

scholarly journals MBNL1 alternative splicing isoforms play opposing roles in cancer

2018 ◽  
Vol 1 (5) ◽  
pp. e201800157 ◽  
Author(s):  
Tommaso Tabaglio ◽  
Diana HP Low ◽  
Winnie Koon Lay Teo ◽  
Pierre Alexis Goy ◽  
Piotr Cywoniuk ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Gene Function ◽  
Dominant Negative ◽  
Individual Gene ◽  
Cancer Types ◽  
Splicing Isoforms ◽  
Isoform Switching ◽  
And Migration

The extent of and the oncogenic role played by alternative splicing (AS) in cancer are well documented. Nonetheless, only few studies have attempted to dissect individual gene function at an isoform level. Here, we focus on the AS of splicing factors during prostate cancer progression, as these factors are known to undergo extensive AS and have the potential to affect hundreds of downstream genes. We identified exon 7 (ex7) in the MBNL1 (Muscleblind-like 1) transcript as being the most differentially included exon in cancer, both in cell lines and in patients' samples. In contrast, MBNL1 overall expression was down-regulated, consistently with its described role as a tumor suppressor. This observation holds true in the majority of cancer types analyzed. We first identified components associated to the U2 splicing complex (SF3B1, SF3A1, and PHF5A) as required for efficient ex7 inclusion and we confirmed that this exon is fundamental for MBNL1 protein homodimerization. We next used splice-switching antisense oligonucleotides (AONs) or siRNAs to compare the effect of MBNL1 splicing isoform switching with knockdown. We report that whereas the absence of MBNL1 is tolerated in cancer cells, the expression of isoforms lacking ex7 (MBNL1 Δex7) induces DNA damage and inhibits cell viability and migration, acting as dominant negative proteins. Our data demonstrate the importance of studying gene function at the level of alternative spliced isoforms and support our conclusion that MBNL1 Δex7 proteins are antisurvival factors with a defined tumor suppressive role that cancer cells tend to down-regulate in favor of MBNL +ex7 isoforms.

How Antimalarials and Antineoplastic Drugs can Interact in Combination Therapies: a Perspective on the Role of PPT1 Enzyme

2021 ◽  
Vol 22 ◽  
Author(s):  
Diana Duarte ◽  
Nuno Vale
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Antineoplastic Agents ◽  
Antimalarial Drugs ◽  
Antineoplastic Drugs ◽  
Anticancer Effects ◽  
Different Types ◽  
Important Pathway ◽  
Palmitoyl Protein Thioesterase

: Antimalarial drugs from different classes have demonstrated anticancer effects in different types of cancer cells, but their complete mode of action in cancer remains unknown. Recently, several studies reported the important role of palmitoyl-protein thioesterase 1 (PPT1), a lysosomal enzyme, as the molecular target of chloroquine and its derivates in cancer. It was also found that PPT1 is overexpressed in different types of cancer, such as breast, colon, etc. Our group has found a synergistic interaction between antimalarial drugs, such as mefloquine, artesunate and chloroquine and antineoplastic drugs in breast cancer cells, but the mechanism of action was not determined. Here, we describe the importance of autophagy and lysosomal inhibitors in tumorigenesis and hypothesize that other antimalarial agents besides chloroquine could also interact with PPT1 and inhibit the mechanistic target of rapamycin (mTOR) signalling, an important pathway in cancer progression. We believe that PPT1 inhibition results in changes in the lysosomal metabolism that result in less accumulation of antineoplastic drugs in lysosomes, which increases the bioavailability of the antineoplastic agents. Taken together, these mechanisms help to explain the synergism of antimalarial and antineoplastic agents in cancer cells.

Mitophagy in Carcinogenesis and Tumor progression- A New paradigm with Emerging Importance

2021 ◽  
Vol 21 ◽  
Author(s):  
Suman K. Ray ◽  
Sukhes Mukherjee
Keyword(s):  
Tumor Progression ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Mammalian Cells ◽  
Mitochondrial Dynamics ◽  
Clinical Importance ◽  
Malignant Cells ◽  
Malignant Growth ◽  
New Paradigm ◽  
Pancreatic Cancer Cells

: The term Mitophagy has been newly concerned in reforming metabolic landscape inside cancerous cells in addition to interface between malignant cells as well as other major constituents of tumor microenvironment. Several profoundly interrelated systems, comprising mitochondrial dynamics and mitophagy, function in mammalian cells as vital mitochondrial regulator process, and their consequence in neoplastic development has newly illuminated clinically. In specific instance of cancer cells, mitochondrialprotected metabolic paths are revamped to meet expanded bioenergetics along with biosynthetic necessities of malignant cells in addition to deal with oxidative stress. It is an exhausting task to foresee the role that mitophagy has on malignant growth cells since it relies upon various elements like cancer variability, malignant growth phase, genetic background and harmony between cell demand and accessibility. As per condition, mitophagy may have a double role as cancer suppressor for example Atg5 (autophagy related 5) or Atg7 (autophagy related 7) or execute promoter like function for instance FUNDC1 (FUN14 domain-containing protein 1), BNIP3 (BCL2/adenovirus E1B 19-kDa-interacting protein 3), PINK1 (PTEN-instigated kinase 1) etc. Tumor suppressive function of Parkin (E3 ubiquitin ligase) is likewise distinguished in mammary gland carcinoma where obstruction of mitophagy impacts tumor progression. In pancreatic cancer cells and in hepatocellular carcinoma hypermethylation of the BNIP3, promoter occurs that prevent HIF-1 (HypoxiaInducible Factor 1) binding besides ensuing initiation of mitophagy. Since the double role mitophagy has in malignant growth relying upon various circumstances and cell varieties, a range of studies have been going on mitophagy and its role in cancer progression and development is opening up a new paradigm with immense clinical importance.

scholarly journals Heat Shock Proteins Are Essential Components in Transformation and Tumor Progression: Cancer Cell Intrinsic Pathways and Beyond

2019 ◽  
Vol 20 (18) ◽  
pp. 4507 ◽  
Author(s):  
Lang ◽  
Guerrero-Giménez ◽  
Prince ◽  
Ackerman ◽  
Bonorino ◽  
...  
Keyword(s):  
Heat Shock ◽  
Cancer Cells ◽  
Stress Proteins ◽  
De Novo ◽  
Human Cancer ◽  
Essential Components ◽  
Wide Range ◽  
Cancer Types ◽  
Shock Proteins

Heat shock protein (HSP) synthesis is switched on in a remarkably wide range of tumor cells, in both experimental animal systems and in human cancer, in which these proteins accumulate in high levels. In each case, elevated HSP concentrations bode ill for the patient, and are associated with a poor outlook in terms of survival in most cancer types. The significance of elevated HSPs is underpinned by their essential roles in mediating tumor cell intrinsic traits such as unscheduled cell division, escape from programmed cell death and senescence, de novo angiogenesis, and increased invasion and metastasis. An increased HSP expression thus seems essential for tumorigenesis. Perhaps of equal significance is the pronounced interplay between cancer cells and the tumor milieu, with essential roles for intracellular HSPs in the properties of the stromal cells, and their roles in programming malignant cells and in the release of HSPs from cancer cells to influence the behavior of the adjacent tumor and infiltrating the normal cells. These findings of a triple role for elevated HSP expression in tumorigenesis strongly support the targeting of HSPs in cancer, especially given the role of such stress proteins in resistance to conventional therapies.

scholarly journals Role of Integrins in Resistance to Therapies Targeting Growth Factor Receptors in Cancer

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 692 ◽  
Author(s):  
Elisabete Cruz da Silva ◽  
Monique Dontenwill ◽  
Laurence Choulier ◽  
Maxime Lehmann
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Tyrosine Kinases ◽  
Treatment Options ◽  
Cancer Cell Proliferation ◽  
Remarkable Feature ◽  
Rtk Signaling ◽  
Intracellular Signal ◽  
New Treatment

Integrins contribute to cancer progression and aggressiveness by activating intracellular signal transduction pathways and transducing mechanical tension forces. Remarkably, these adhesion receptors share common signaling networks with receptor tyrosine kinases (RTKs) and support their oncogenic activity, thereby promoting cancer cell proliferation, survival and invasion. During the last decade, preclinical studies have revealed that integrins play an important role in resistance to therapies targeting RTKs and their downstream pathways. A remarkable feature of integrins is their wide-ranging interconnection with RTKs, which helps cancer cells to adapt and better survive therapeutic treatments. In this context, we should consider not only the integrins expressed in cancer cells but also those expressed in stromal cells, since these can mechanically increase the rigidity of the tumor microenvironment and confer resistance to treatment. This review presents some of these mechanisms and outlines new treatment options for improving the efficacy of therapies targeting RTK signaling.

scholarly journals Spatiotemporal pH Heterogeneity as a Promoter of Cancer Progression and Therapeutic Resistance

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1026 ◽  
Author(s):  
David E. Korenchan ◽  
Robert R. Flavell
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Co2 Exchange ◽  
Therapeutic Resistance ◽  
Slow Time ◽  
Phenotypic Changes ◽  
Ph Buffering ◽  
Available Technology ◽  
Kinetics Of

Dysregulation of pH in solid tumors is a hallmark of cancer. In recent years, the role of altered pH heterogeneity in space, between benign and aggressive tissues, between individual cancer cells, and between subcellular compartments, has been steadily elucidated. Changes in temporal pH-related processes on both fast and slow time scales, including altered kinetics of bicarbonate-CO2 exchange and its effects on pH buffering and gradual, progressive changes driven by changes in metabolism, are further implicated in phenotypic changes observed in cancers. These discoveries have been driven by advances in imaging technologies. This review provides an overview of intra- and extracellular pH alterations in time and space reflected in cancer cells, as well as the available technology to study pH spatiotemporal heterogeneity.

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