EpCAM as Modulator of Tissue Plasticity

Fagotto, François

doi:10.3390/cells9092128

Cited by 10 publications

(10 citation statements)

References 63 publications

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“…EpCAM serves mainly as a homophilic cell adhesion molecule, but it has also been linked to roles in proliferation, differentiation, and cell-migration with differing levels of expression [ 113 ]. In the early stages of embryonic development, EpCAM is not expressed solely by epithelial cells, indicating a greater role of EpCAM plasticity and early development, and through the use of knock-out studies in Zebrafish, loss of EpCAM is linked to lethality and loss of tissue integrity, displaying the dual role of EpCAM in adhesion and motility [ 114 , 115 ]. EpCAM also plays a role in the assembly of adherens junctions as shown by the dramatic decrease in mRNA and protein expression of nectin1, a molecule involved in regulating the assembly of adherens and tight junctions, in EpCAM mutant mice [ 116 ].…”

Section: Overview On Oncogenic Emt: Emt-associated Biomarkersmentioning

confidence: 99%

The Role of RKIP in the Regulation of EMT in the Tumor Microenvironment

Cessna

Baritaki

Zaravinos

et al. 2022

Cancers

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The Raf Kinase Inhibitor Protein (RKIP) is a unique gene product that directly inhibits the Raf/Mek/Erk and NF-kB pathways in cancer cells and resulting in the inhibition of cell proliferation, viability, EMT, and metastasis. Additionally, RKIP is involved in the regulation of cancer cell resistance to both chemotherapy and immunotherapy. The low expression of RKIP expression in many cancer types is responsible, in part, for the pathogenesis of cancer and its multiple properties. The inhibition of EMT and metastasis by RKIP led to its classification as a tumor suppressor. However, the mechanism by which RKIP mediates its inhibitory effects on EMT and metastases was not clear. We have proposed that one mechanism involves the negative regulation by RKIP of the expression of various gene products that mediate the mesenchymal phenotype as well as the positive regulation of gene products that mediate the epithelial phenotype via signaling cross talks between RKIP and each gene product. We examined several EMT mesenchymal gene products such as Snail, vimentin, N-cadherin, laminin and EPCAM and epithelial gene products such as E-cadherin and laminin. We have found that indeed these negative and positive correlations were detected in the signaling cross-talks. In addition, we have also examined bioinformatic data sets on different human cancers and the findings corroborated, in large part, the findings observed in the signaling cross-talks with few exceptions in some cancer types. The overall findings support the underlying mechanism by which the tumor suppressor RKIP regulates the expression of gene products involved in EMT and metastasis. Hence, the development of agent that can selectively induce RKIP expression in cancers with low expressions should result in the activation of the pleiotropic anti-cancer activities of RKIP and resulting in multiple effects including inhibition of tumor cell proliferation, EMT, metastasis and sensitization of resistant tumor cells to respond to both chemotherapeutics and immunotherapeutics.

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Section: Overview On Oncogenic Emt: Emt-associated Biomarkersmentioning

confidence: 99%

The Role of RKIP in the Regulation of EMT in the Tumor Microenvironment

Cessna

Baritaki

Zaravinos

et al. 2022

Cancers

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“…EpCAM is related to several signaling pathways including the intramembrane protein hydrolysis (RIP)-mediated signaling and the activation of Wnt signaling to impact on tumor cell proliferation [ 41 ]. Today, EpCAM is reckoned as a marker highly expressed in carcinomas and extremely correlated with poor prognosis [ 42 ]. A large retrospective study using tissue microarrays showed that high level of EpCAM expression was found in 94.1% of patients with lung, colon, and prostate cancers and observed a significant reverse correlation between EpCAM expression and survival time [ 43 ].…”

Section: Targeting Antigensmentioning

confidence: 99%

Recent advances and challenges of bispecific antibodies in solid tumors

Zhu

et al. 2021

Exp Hematol Oncol

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Cancer immunotherapy has made remarkable progress in the past decade. Bispecific antibodies (BsAbs) have acquired much attention as the next generation strategy of antibody-target cancer immunotherapy, which overwhelmingly focus on T cell recruitment and dual receptors blockade. So far, BsAb drugs have been proved clinically effective and approved for the treatment of hematologic malignancies, but no BsAb have been approved in solid tumors. Numerous designed BsAb drugs for solid tumors are now undergoing evaluation in clinical trials. In this review, we will introduce the formats of bispecific antibodies, and then update the latest preclinical studies and clinical trials in solid tumors of BsAbs targeting EpCAM, CEA, PMSA, ErbB family, and so on. Finally, we discuss the BsAb-related adverse effects and the alternative strategy for future study.

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“…Benign epithelia express EpCAM at a variable but generally lower level compared with carcinoma cells ( 41 ). EpCAM can modulate cell migration, proliferation and differentiation, and also prevent cell-cell adhesion ( 42 , 43 ). Vimentin is a well-known marker of EMT ( 44 , 45 ).…”

Section: Discussionmentioning

confidence: 99%

Bladder cancer cell lines adapt their aggressiveness profile to oxygen tension

et al. 2022

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During the process of tumor growth, cancer cells will be subjected to intermittent hypoxia. This results from the delay in the development of the vascular network in relation to the proliferation of cancer cells. The hypoxic nature of a tumor has been demonstrated as a negative factor for patient survival. To evaluate the impact of hypoxia on the survival and migration properties of low and high-grade bladder cancer cell lines, two low-grade (MGHU-3 and SW-780) and two high-grade (SW-1710 and T24) bladder cancer cell lines were cultured in normoxic (20% O 2 ) or hypoxic atmospheric conditions (2% O 2 ). The response of bladder cancer cell lines to hypoxic atmospheric cell culture conditions was examined under several parameters, including epithelial-mesenchymal transition, doubling time and metabolic activities, thrombospondin-1 expression, whole Matrix Metallo-Proteinase activity, migration and resistance to oxidative stress. The low-grade cell line response to hypoxia was heterogeneous even if it tended to adopt a more aggressive profile. Hypoxia enhanced migration and pro-survival properties of MGHU-3 cells, whereas these features were reduced for the SW-780 cell line cultured under low oxygen tension. The responses of tested high-grade cell lines were more homogeneous and tended to adopt a less aggressive profile. Hypoxia drastically changed some of the bladder cancer cell line properties, for example matrix metalloproteinases expression for all cancer cells but also switch in glycolytic metabolism of low grade cancer cells. Overall, studying bladder cancer cells in hypoxic environments are relevant for the translation from in vitro findings to in vivo context.

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EpCAM as Modulator of Tissue Plasticity

Cited by 10 publications

References 63 publications

The Role of RKIP in the Regulation of EMT in the Tumor Microenvironment

The Role of RKIP in the Regulation of EMT in the Tumor Microenvironment

Recent advances and challenges of bispecific antibodies in solid tumors

Bladder cancer cell lines adapt their aggressiveness profile to oxygen tension

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