Prominin-2 and Other Relatives of CD133

Fargeas, Christine A.

doi:10.1007/978-1-4614-5894-4_2

Cited by 11 publications

(8 citation statements)

References 53 publications

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“…Moreover, PROM1+ ovarian CSCs are highly tumorigenic, chemoresistant, and metastatic and they promote the adhesion capabilities of the ovarian cancer metastatic niche [57]. In contrast, our analysis showed that PROM2 is overexpressed in breast and lung cancers, and this result is in agreement with those of previous genome profiling studies and studies on expressed sequence tag (EST) clones deposited in the GenBank database [58,59]. Thus, these results imply that prominins may be either oncogenes or tumor suppressor genes, depending on the type of cancer.…”

Section: Prominin Mrna Expression Analysissupporting

confidence: 91%

PROM1 and PROM2 expression differentially modulates clinical prognosis of cancer: a multiomics analysis

et al. 2019

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Prominin 1 (PROM1) is considered a biomarker for cancer stem cells, although its biological role is unclear. Prominin 2 (PROM2) has also been associated with certain cancers. However, the prognostic value of PROM1 and PROM2 in cancer is controversial. Here, we performed a systematic data analysis to examine whether prominins can function as prognostic markers in human cancers. The expression of prominins was assessed and their prognostic value in human cancers was determined using univariate and multivariate survival analyses, via various online platforms. We selected a group of prominent functional protein partners of prominins by protein-protein interaction analysis. Subsequently, we investigated the relationship between mutations and copy number alterations in prominin genes and various types of cancers. Furthermore, we identified genes that correlated with PROM1 and PROM2 in certain cancers, based on their levels of expression. Gene ontology and pathway analyses were performed to assess the effect of these correlated genes on various cancers. We observed that PROM1 was frequently overexpressed in esophageal, liver, and ovarian cancers and its expression was negatively associated with prognosis, whereas PROM2 overexpression was associated with poor overall survival in lung and ovarian cancers. Based on the varying characteristics of prominins, we conclude that PROM1 and PROM2 expression differentially modulates the clinical outcomes of cancers.

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Section: Prominin Mrna Expression Analysissupporting

confidence: 91%

PROM1 and PROM2 expression differentially modulates clinical prognosis of cancer: a multiomics analysis

et al. 2019

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“…It is the first member of the pentaspan membrane glycoprotein prominin family, which is expressed throughout the animal kingdom [3]–[5]. Human prominin -1 as detected by the widely used monoclonal antibody (mAb) AC133 [6] marks numerous somatic stem and progenitor cells originating from various tissues and organs [4], [7]–[10].…”

Section: Introductionmentioning

confidence: 99%

Human Prominin-1 (CD133) Is Detected in Both Neoplastic and Non-Neoplastic Salivary Gland Diseases and Released into Saliva in a Ubiquitinated Form

et al. 2014

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Prominin-1 (CD133) is physiologically expressed at the apical membranes of secretory (serous and mucous) and duct cells of major salivary glands. We investigated its expression in various human salivary gland lesions using two distinct anti-prominin-1 monoclonal antibodies (80B258 and AC133) applied on paraffin-embedded sections and characterized its occurrence in saliva. The 80B258 epitope was extensively expressed in adenoid cystic carcinoma, in lesser extent in acinic cell carcinoma and pleomorphic adenoma, and rarely in mucoepidermoid carcinoma. The 80B258 immunoreactivity was predominately detected at the apical membrane of tumor cells showing acinar or intercalated duct cell differentiation, which lined duct- or cyst-like structures, and in luminal secretions. It was observed on the whole cell membrane in non-luminal structures present in the vicinity of thin-walled blood vessels and hemorrhagic areas in adenoid cystic carcinoma. Of note, AC133 labeled only a subset of 80B258–positive structures. In peritumoral salivary gland tissues as well as in obstructive sialadenitis, an up-regulation of prominin-1 (both 80B258 and AC133 immunoreactivities) was observed in intercalated duct cells. In most tissues, prominin-1 was partially co-expressed with two cancer markers: carcinoembryonic antigen (CEA) and mucin-1 (MUC1). Differential centrifugation of saliva followed by immunoblotting indicated that all three markers were released in association with small membrane vesicles. Immuno-isolated prominin-1–positive vesicles contained CEA and MUC1, but also exosome-related proteins CD63, flotillin-1, flotillin-2 and the adaptor protein syntenin-1. The latter protein was shown to interact with prominin-1 as demonstrated by its co-immunoisolation. A fraction of saliva-associated prominin-1 appeared to be ubiquitinated. Collectively, our findings bring new insights into the biochemistry and trafficking of prominin-1 as well as its immunohistochemical profile in certain types of salivary gland tumors and inflammatory diseases.

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“…Although both genes display a higher degree of compactness compared to prom1 (Table S1), they do not show a conserved synteny (11). Still, prom3 might have evolved from the same ancestral locus as prom2 generated during the first round of vertebrate genome duplication (11,12,91).…”

Section: Discussionmentioning

confidence: 99%

Prominins control ciliary length throughout the animal kingdom: New lessons from human prominin-1 and zebrafish prominin-3

Jászai

Thamm

Karbanová

et al. 2020

Journal of Biological Chemistry

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Prominins (proms) are transmembrane glycoproteins conserved throughout the animal kingdom. They are associated with plasma membrane protrusions, such as primary cilia, as well as extracellular vesicles derived thereof. Primary cilia host numerous signaling pathways affected in diseases known as ciliopathies. Human PROM1 (CD133) is detected in both somatic and cancer stem cells and is also expressed in terminally differentiated epithelial and photoreceptor cells. Genetic mutations in the PROM1 gene result in retinal degeneration by impairing the proper formation of the outer segment of photoreceptors, a modified cilium. Here, we investigated the impact of proms on two distinct examples of ciliogenesis. First, we demonstrate that the overexpression of a dominant-negative mutant variant of human PROM1 (i.e. mutation Y819F/Y828F) significantly decreases ciliary length in Madin–Darby canine kidney cells. These results contrast strongly to the previously observed enhancing effect of WT PROM1 on ciliary length. Mechanistically, the mutation impeded the interaction of PROM1 with ADP-ribosylation factor–like protein 13B, a key regulator of ciliary length. Second, we observed that in vivo knockdown of prom3 in zebrafish alters the number and length of monocilia in the Kupffer's vesicle, resulting in molecular and anatomical defects in the left-right asymmetry. These distinct loss-of-function approaches in two biological systems reveal that prom proteins are critical for the integrity and function of cilia. Our data provide new insights into ciliogenesis and might be of particular interest for investigations of the etiologies of ciliopathies.

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Prominin-2 and Other Relatives of CD133

Cited by 11 publications

References 53 publications

PROM1 and PROM2 expression differentially modulates clinical prognosis of cancer: a multiomics analysis

PROM1 and PROM2 expression differentially modulates clinical prognosis of cancer: a multiomics analysis

Human Prominin-1 (CD133) Is Detected in Both Neoplastic and Non-Neoplastic Salivary Gland Diseases and Released into Saliva in a Ubiquitinated Form

Prominins control ciliary length throughout the animal kingdom: New lessons from human prominin-1 and zebrafish prominin-3

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