scholarly journals Golgi Phosphoprotein 73: The Driver of Epithelial-Mesenchymal Transition in Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yiming Liu ◽  
Xinyang Hu ◽  
Shiyao Liu ◽  
Sining Zhou ◽  
Zhi Chen ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Secretory Protein ◽  
Multifunctional Protein ◽  
Mesenchymal Transition ◽  
Functional Roles ◽  
Research Fields ◽  
Cancer Tissues ◽  
Related Proteins

Golgi phosphoprotein 73 (GP73, also termed as GOLM1 or GOLPH2) is a glycosylated protein residing on cis-Golgi cisternae and highly expressed in various types of cancer tissues. Since GP73 is a secretory protein and detectable in serum derived from cancer patients, it has been regarded as a novel serum biomarker for the diagnosis of different cancers, especially hepatocellular carcinoma (HCC). However, the functional roles of GP73 in cancer development are still poorly understood. In recent years, it has been discovered that GP73 acts as a multifunctional protein-facilitating cancer progression, and strikingly, it has been identified as a leading factor promoting epithelial-mesenchymal transition (EMT) of cancer cells and causing cancer metastasis. In this review, we have overviewed the latest findings of the functional roles of GP73 in elevating cancer progression, especially in facilitating EMT and cancer metastasis through modulating expression, transactivation, and trafficking of EMT-related proteins. In addition, unsolved research fields of GP73 have been lightened, which might be helpful to elucidate the regulatory mechanisms of GP73 on EMT and provide potential approaches in therapeutics against cancer metastasis.

scholarly journals TRIM50 Suppresses Pancreatic Cancer Progression and Reverses the Epithelial-Mesenchymal Transition via Facilitating the Ubiquitous Degradation of Snail1

2021 ◽  
Vol 11 ◽  
Author(s):  
Rongkun Li ◽  
Lili Zhu ◽  
Yangxizi Peng ◽  
Xiaoxin Zhang ◽  
Chunhua Dai ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Development ◽  
Poor Survival ◽  
Mesenchymal Transition ◽  
Functional Roles ◽  
Pancreatic Cancer Cells ◽  
Tripartite Motif ◽  
Cancer Tissues

Emerging evidence suggests that the tripartite motif (TRIM) family play important roles in tumor development and progression. Tripartite motif-containing 50 (TRIM50) is a member of the TRIM family, but little is known regarding its expression and potential functional roles in cancer. In this study, we first analyzed the expression pattern and clinical significance of TRIM50 in pancreatic cancer and found that TRIM50 expression is significantly reduced in pancreatic cancer tissues and its downregulation is associated with poor survival for pancreatic cancer patients. Functionally, TRIM50 overexpression in pancreatic cancer cells decreases their proliferation and motility capabilities and reverses the epithelial-mesenchymal transition (EMT) process, whereas TRIM50 depletion had the opposite effects. Mechanically, TRIM50 directly interacts with Snail1, a key regulator of EMT, and acts as an E3 ubiquitin ligase to target Snail1 for ubiquitous degradation. The function of TRIM50 in suppressing cell migration and EMT depends on TRIM50-promoted Snail1 degradation. In conclusion, our findings identify TRIM50 as a tumor suppressor that inhibits pancreatic cancer progression and reverses EMT via degrading Snail1 and provide new insights into the progression of pancreatic cancer.

scholarly journals Tumor-Derived Exosomes Mediate the Instability of Cadherins and Promote Tumor Progression

2019 ◽  
Vol 20 (15) ◽  
pp. 3652 ◽  
Author(s):  
Bowen Wang ◽  
Zengqi Tan ◽  
Feng Guan
Keyword(s):  
Cancer Progression ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Development ◽  
Intercellular Junctions ◽  
Bioactive Molecules ◽  
Aberrant Expression ◽  
Altered Expression ◽  
Mesenchymal Transition ◽  
Related Proteins

Cadherins, including E-cadherin, N-cadherin, VE-cadherin, etc., are important adhesion molecules mediating intercellular junctions. The abnormal expression of cadherins is often associated with tumor development and progression. Epithelial–mesenchymal transition (EMT) is the most important step in the metastasis cascade and is accompanied by altered expression of cadherins. Recent studies reveal that as a cargo for intercellular communication, exosomes—one type of extracellular vesicles that can be secreted by tumor cells—are involved in a variety of physiological and pathological processes, especially in tumor metastasis. Tumor-derived exosomes play a crucial role in mediating the cadherin instability in recipient cells by transferring bioactive molecules (oncogenic microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), EMT-related proteins, and others), modulating their local and distant microenvironment, and facilitating cancer metastasis. In turn, aberrant expression of cadherins in carcinoma cells can also affect the biogenesis and release of exosomes. Therefore, we summarize the current research on the crosstalk between tumor-derived exosomes and aberrant cadherin signals to reveal the unique role of exosomes in cancer progression.

Galectin-3: A factotum in carcinogenesis bestowing an archery for prevention

Tumor Biology ◽  
2021 ◽  
Vol 43 (1) ◽  
pp. 77-96
Author(s):  
T. Jeethy Ram ◽  
Asha Lekshmi ◽  
Thara Somanathan ◽  
K. Sujathan
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Therapy Resistance ◽  
Cellular Level ◽  
Clinical Samples ◽  
Innovative Strategy ◽  
Mesenchymal Transition ◽  
Galectin 3

Cancer metastasis and therapy resistance are the foremost hurdles in oncology at the moment. This review aims to pinpoint the functional aspects of a unique multifaceted glycosylated molecule in both intracellular and extracellular compartments of a cell namely galectin-3 along with its metastatic potential in different types of cancer. All materials reviewed here were collected through the search engines PubMed, Scopus, and Google scholar. Among the 15 galectins identified, the chimeric gal-3 plays an indispensable role in the differentiation, transformation, and multi-step process of tumor metastasis. It has been implicated in the molecular mechanisms that allow the cancer cells to survive in the intravascular milieu and promote tumor cell extravasation, ultimately leading to metastasis. Gal-3 has also been found to have a pivotal role in immune surveillance and pro-angiogenesis and several studies have pointed out the importance of gal-3 in establishing a resistant phenotype, particularly through the epithelial-mesenchymal transition process. Additionally, some recent findings suggest the use of gal-3 inhibitors in overcoming therapeutic resistance. All these reports suggest that the deregulation of these specific lectins at the cellular level could inhibit cancer progression and metastasis. A more systematic study of glycosylation in clinical samples along with the development of selective gal-3 antagonists inhibiting the activity of these molecules at the cellular level offers an innovative strategy for primary cancer prevention.

scholarly journals Cooperation of Cancer Stem Cell Properties and Epithelial-Mesenchymal Transition in the Establishment of Breast Cancer Metastasis

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Tetsu Hayashida ◽  
Hiromitsu Jinno ◽  
Yuko Kitagawa ◽  
Masaki Kitajima
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Tumor ◽  
Breast Cancer Metastasis ◽  
Cell Junctions ◽  
Mesenchymal Transition

Epithelial-mesenchymal transition (EMT) is a multistep process in which cells acquire molecular alterations such as loss of cell-cell junctions and restructuring of the cytoskeleton. There is an increasing understanding that this process may promote breast cancer progression through promotion of invasive and metastatic tumor growth. Recent observations imply that there may be a cross-talk between EMT and cancer stem cell properties, leading to enhanced tumorigenicity and the capacity to generate heterogeneous tumor cell populations. Here, we review the experimental and clinical evidence for the involvement of EMT in cancer stem cell theory, focusing on the common characteristics of this phenomenon.

scholarly journals Orai3 Regulates Pancreatic Cancer Metastasis by Encoding a Functional Store Operated Calcium Entry Channel

2021 ◽  
Author(s):  
Samriddhi Arora ◽  
Jyoti Tanwar ◽  
Nutan Sharma ◽  
Suman Saurav ◽  
Rajender K. Motiani
Keyword(s):  
Pancreatic Cancer ◽  
Survival Time ◽  
Cell Lines ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Mesenchymal Transition

Pancreatic cancer (PC) is one of the most lethal forms of cancers with 5-year mean survival rate of less than 10%. Most of the PC associated deaths are due to metastasis to secondary sites. Calcium (Ca2+) signaling plays a critical role in regulating hallmarks of cancer progression including cell proliferation, migration and apoptotic resistance. Store operated Ca2+ entry (SOCE) mediated by Orai1/2/3 channels is a highly regulated and ubiquitous pathway responsible for Ca2+ influx into non-excitable cells. In this study, we performed extensive bioinformatic analysis of publicly available datasets and observed that Orai3 expression is inversely associated with the mean survival time of PC patients. Orai3 expression analysis in a battery of PC cell lines corroborated its differential expression profile. We then carried out thorough Ca2+ imaging experiments in 6 PC cell lines and found that Orai3 forms a functional SOCE in PC cells. Our in vitro functional assays show that Orai3 regulates PC cell cycle progression, apoptosis and migration. Most importantly, our in vivo xenograft studies demonstrate a critical role of Orai3 in PC tumor growth and secondary metastasis. Mechanistically, Orai3 controls G1 phase progression, matrix metalloproteinase expression and epithelial-mesenchymal transition in PC cells. Taken together, this study for the first time reports that Orai3 drives aggressive phenotypes of PC cells i.e. migration in vitro and metastasis in vivo. Considering that Orai3 expression is inversely associated with the PC patients survival time, it appears to be a highly attractive therapeutic target.

scholarly journals Hybrid Epithelial/Mesenchymal State in Cancer Metastasis: Clinical Significance and Regulatory Mechanisms

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 623 ◽  
Author(s):  
Tsai-Tsen Liao ◽  
Muh-Hwa Yang
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Normal Tissue ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Regulatory Mechanisms ◽  
Dynamic Changes ◽  
Mesenchymal Transition ◽  
Stressful Environment ◽  
Metastatic Process

Epithelial-mesenchymal transition (EMT) has been well recognized for its essential role in cancer progression as well as normal tissue development. In cancer cells, activation of EMT permits the cells to acquire migratory and invasive abilities and stem-like properties. However, simple categorization of cancer cells into epithelial and mesenchymal phenotypes misleads the understanding of the complicated metastatic process, and contradictory results from different studies also indicate the limitation of application of EMT theory in cancer metastasis. Nowadays, growing evidence suggests the existence of an intermediate status between epithelial and mesenchymal phenotypes, i.e., the “hybrid epithelial-mesenchymal (hybrid E/M)” state, provides a possible explanation for those conflicting results. Appearance of hybrid E/M phenotype offers a more plastic status for cancer cells to adapt the stressful environment for proceeding metastasis. In this article, we review the biological importance of the dynamic changes between the epithelial and the mesenchymal states. The regulatory mechanisms encompassing the translational, post-translational, and epigenetic control for this complex and plastic status are also discussed.

scholarly journals Gelsolin Promotes Cancer Progression by Regulating Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma and Correlates with a Poor Prognosis

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Yixi Zhang ◽  
Xiaojing Luo ◽  
Jianwei Lin ◽  
Shunjun Fu ◽  
Pei Feng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Disease Free Survival ◽  
Tumour Cells ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Gelsolin (GSN), a cytoskeletal protein, is frequently overexpressed in different cancers and promotes cell motility. The biological function of GSN in hepatocellular carcinoma (HCC) and its mechanism remain unclear. The expression of GSN was assessed in a cohort of 188 HCC patients. The effects of GSN on the migration and invasion of tumour cells were examined. Then, the role of GSN in tumour growth in vivo was determined by using a cancer metastasis assay. The possible mechanism by which GSN promotes HCC progression was explored. As a result, GSN was overexpressed in HCC tissues. High GSN expression was significantly correlated with late Edmondson grade, encapsulation, and multiple tumours. Patients with high GSN expression had worse overall survival (OS) and disease-free survival (DFS) than those with low GSN expression. GSN expression was identified as an independent risk factor in both OS (hazard risk (HR) = 1.620, 95% confidence interval (CI) = 1.105–2.373, P<0.001) and DFS (HR = 1.744, 95% CI = 1.205–2.523, P=0.003). Moreover, GSN knockdown significantly inhibited the migration and invasion of HCC tumour cells, while GSN overexpression attenuated these effects by regulating epithelial-mesenchymal transition (EMT) In conclusion, GSN promotes cancer progression and is associated with a poor prognosis in HCC patients. GSN promotes HCC progression by regulating EMT.

scholarly journals ChrXq27.3 miRNA cluster functions in cancer development

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Kosuke Yoshida ◽  
Akira Yokoi ◽  
Yusuke Yamamoto ◽  
Hiroaki Kajiyama
Keyword(s):  
Cancer Progression ◽  
Target Genes ◽  
Epithelial Mesenchymal Transition ◽  
Mature Mirnas ◽  
Mirna Cluster ◽  
Mesenchymal Transition ◽  
Normal Tissues ◽  
Mirna Clusters ◽  
Cancer Tissues ◽  
Encoding Genes

AbstractMicroRNAs (miRNAs) regulate the expression of their target genes post-transcriptionally; thus, they are deeply involved in fundamental biological processes. miRNA clusters contain two or more miRNA-encoding genes, and these miRNAs are usually coexpressed due to common expression mechanisms. Therefore, miRNA clusters are effective modulators of biological pathways by the members coordinately regulating their multiple target genes, and an miRNA cluster located on the X chromosome q27.3 region has received much attention in cancer research recently. In this review, we discuss the novel findings of the chrXq27.3 miRNA cluster in various types of cancer.The chrXq27.3 miRNA cluster contains 30 mature miRNAs synthesized from 22 miRNA-encoding genes in an ~ 1.3-Mb region. The expressions of these miRNAs are usually negligible in many normal tissues, with the male reproductive system being an exception. In cancer tissues, each miRNA is dysregulated, compared with in adjacent normal tissues. The miRNA-encoding genes are not uniformly distributed in the region, and they are further divided into two groups (the miR-506-514 and miR-888-892 groups) according to their location on the genome. Most of the miRNAs in the former group are tumor-suppressive miRNAs that are further downregulated in various cancers compared with normal tissues. miR-506-3p in particular is the most well-known miRNA in this cluster, and it has various tumor-suppressive functions associated with the epithelial–mesenchymal transition, proliferation, and drug resistance. Moreover, other miRNAs, such as miR-508-3p and miR-509-3p, have similar tumor-suppressive effects. Hence, the expression of these miRNAs is clinically favorable as prognostic factors in various cancers. However, the functions of the latter group are less understood. In the latter group, miR-888-5p displays oncogenic functions, whereas miR-892b is tumor suppressive. Therefore, the functions of the miR-888–892 group are considered to be cell type- or tissue-specific.In conclusion, the chrXq27.3 miRNA cluster is a critical regulator of cancer progression, and the miRNAs themselves, their regulatory mechanisms, and their target genes might be promising therapeutic targets.

scholarly journals Dynamics of Phenotypic Heterogeneity Associated with EMT and Stemness during Cancer Progression

2019 ◽  
Vol 8 (10) ◽  
pp. 1542 ◽  
Author(s):  
Mohit Kumar Jolly ◽  
Toni Celià-Terrassa
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Relevant Literature ◽  
Phenotypic Heterogeneity ◽  
State Transitions ◽  
Strong Impact ◽  
Mesenchymal Transition ◽  
Cancer Aggressiveness

Genetic and phenotypic heterogeneity contribute to the generation of diverse tumor cell populations, thus enhancing cancer aggressiveness and therapy resistance. Compared to genetic heterogeneity, a consequence of mutational events, phenotypic heterogeneity arises from dynamic, reversible cell state transitions in response to varying intracellular/extracellular signals. Such phenotypic plasticity enables rapid adaptive responses to various stressful conditions and can have a strong impact on cancer progression. Herein, we have reviewed relevant literature on mechanisms associated with dynamic phenotypic changes and cellular plasticity, such as epithelial–mesenchymal transition (EMT) and cancer stemness, which have been reported to facilitate cancer metastasis. We also discuss how non-cell-autonomous mechanisms such as cell–cell communication can lead to an emergent population-level response in tumors. The molecular mechanisms underlying the complexity of tumor systems are crucial for comprehending cancer progression, and may provide new avenues for designing therapeutic strategies.

scholarly journals TIPE1 Suppresses Growth and Metastasis of Ovarian Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Zhenyu Zhang ◽  
Minghui Chang ◽  
Xingguo Song ◽  
Kangyu Wang ◽  
Wenjuan Sun ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Cervix Uteri ◽  
Human Tissues ◽  
Mesenchymal Transition ◽  
Normal Human ◽  
Cancer Tissues

TIPE1, a newly identified member in TIPE (TNFAIP8) family, plays an important role in tumorigenesis and immune regulation, but its role in ovarian cancer, especially in tumor metastasis, remains unknown. In the current study, we aimed to reveal the protein expression spectrum of TIPE1 in normal human tissues and explored its relationship with metastasis in ovarian cancer. The results of IHC staining showed that TIPE1 protein was not only detected in cytoplasm in most human tissues but also expressed in both cytoplasm and nucleus in squamous epithelium and some epithelial-derived cells with secretory functions, such as esophagus, cervix uteri and ovary, and thyroid gland. Moreover, TIPE1 protein was downregulated in ovarian cancer tissues compared with that in the paracancerous. More importantly, TIPE1 suppressed tumorigenesis and metastasis of ovarian cancer in vitro and in vivo, as evidence shows its ability to suppress growth, colony formation, migration, and epithelial-mesenchymal transition (EMT) of ovarian cancer. Taken together, our results demonstrate the suppressor role of TIPE1 in ovarian cancer metastasis, indicating TIPE1 might be a metastasis predictor and a novel therapeutic target for ovarian cancer.

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