Suppression of FUT1 attenuates cell proliferation in the HER2-overexpressing cancer cell line NCI-N87

Kawai, Shinya; Kato, Shunsuke; Imai, Hiroo; Okada, Yukinori; Ishioka, Chikashi

doi:10.3892/or.2012.2120

Cited by 29 publications

(30 citation statements)

References 28 publications

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“…49, 50 In addition, the role of autophagy in tumor suppression by preventing the accumulation of damaged organelles and macromolecules 49, 51 further supports our notion that the positive impacts of α 1,2-fucosylation on tumorigenesis may be partially attributable to its negative effect on autophagy. Although it is known that the α 1,2-fucosylated LeY antigens can promote cell proliferation and tumorigenesis by activating EGFR/MAPK signaling, 52, 53 our finding may offer yet another pathway in which α 1,2-fucosylated LAMP-1 and 2 may regulate autophagy biogenesis, thereby influencing tumor development and progression.…”

Section: Discussionmentioning

confidence: 69%

Fucosylation of LAMP-1 and LAMP-2 by FUT1 correlates with lysosomal positioning and autophagic flux of breast cancer cells

Tan

Cho

et al. 2016

Cell Death Dis

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Alpha1,2-fucosyltransferases, FUT1 and FUT2, which transfer fucoses onto the terminal galactose of N-acetyl-lactosamine via α1,2-linkage have been shown to be highly expressed in various types of cancers. A few studies have shown the involvement of FUT1 substrates in tumor cell proliferation and migration. Lysosome-associated membrane protein 1, LAMP-1, has been reported to carry alpha1,2-fucosylated Lewis Y (LeY) antigens in breast cancer cells, however, the biological functions of LeY on LAMP-1 remain largely unknown. Whether or not its family member, LAMP-2, displays similar modifications and functions as LAMP-1 has not yet been addressed. In this study, we have presented evidence supporting that both LAMP-1 and 2 are substrates for FUT1, but not FUT2. We have also demonstrated the presence of H2 and LeY antigens on LAMP-1 by a targeted nanoLC-MS3 and the decreased levels of fucosylation on LAMP-2 by MALDI-TOF analysis upon FUT1 knockdown. In addition, we found that the expression of LeY was substantial in less invasive ER+/PR+/HER− breast cancer cells (MCF-7 and T47D) but negligible in highly invasive triple-negative MDA-MB-231 cells, of which LeY levels were correlated with the levels of LeY carried by LAMP-1 and 2. Intriguingly, we also observed a striking change in the subcellular localization of lysosomes upon FUT1 knockdown from peripheral distribution of LAMP-1 and 2 to a preferential perinuclear accumulation. Besides that, knockdown of FUT1 led to an increased rate of autophagic flux along with diminished activity of mammalian target of rapamycin complex 1 (mTORC1) and enhanced autophagosome–lysosome fusion. This may be associated with the predominantly perinuclear distribution of lysosomes mediated by FUT1 knockdown as lysosomal positioning has been reported to regulate mTOR activity and autophagy. Taken together, our results suggest that downregulation of FUT1, which leads to the perinuclear localization of LAMP-1 and 2, is correlated with increased rate of autophagic flux by decreasing mTOR signaling and increasing autolysosome formation.

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Section: Discussionmentioning

confidence: 69%

Fucosylation of LAMP-1 and LAMP-2 by FUT1 correlates with lysosomal positioning and autophagic flux of breast cancer cells

Tan

Cho

et al. 2016

Cell Death Dis

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“…FUT1, which encodes α1, 2-fucosyltransferase and transfers a fucose residue to galactose, is of key significance to the biosynthesis of Lewis Y antigen [32]. Up-regulated Lewis Y has been found in various tumors including breast, ovarian, and colorectal cancer [33][34][35], leading to tumor growth acceleration and lymph node metastasis through activating ErbB signaling [36]. To our knowledge, FUT1 is for the first time to be demonstrated as the target of miR-34a.…”

Section: Discussionmentioning

confidence: 94%

MiR-34a suppresses HNSCC growth through modulating cell cycle arrest and senescence

Wang¹,

Chen²,

Chen³

et al. 2017

neo

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MiR-34a acts as a tumor suppressor in various malignancies. In HNSCC, the role of miR-34a in proliferation has not been fully elaborated and the target genes are still bind. Here, we addressed that forced miR-34a expression induced cell cycle arrest and senescence. Hypoxia/HIF1α was found to negatively correlate to the expression of miR-34a in HNSCC tissues and partially reverse miR-34a-imposed cell senescence through suppressing miR-34a expression. In order to screen the possible target genes of miR-34a in HNSCC, the differential genes mediated by miR-34a were screened by mRNA microarray. There were 91 genes co-down regulated in two cell lines, which were closely associated with MAPK, ErbB and p53 pathways. Genes, including FUT1, AXL, and MAP2K1 were finally identified as the novel targets of miR-34a by qPCR and luciferase assay. These findings indicate that miR-34a plays an essential role in suppressing HNSCC growth through inducing cell cycle arrest and senescence, by targeting proliferation-associated genes.

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“…For example, increased expression of FUT1 has been associated with increased propensity to metastasize in melanoma and advanced stage in ovarian cancer, while downregulation of FUT1 in a HER2-positive breast cancer cell line decreased proliferation [92–94]. DNA variants in FUT2 has been associated with increased risk of oral cancer in individuals who smoke and/or chew betel quid while in pancreatic cancer, secretor status was not associated with risk [95,96].…”

Section: Modification Of Abo Phenotypesmentioning

confidence: 99%

The role of the histoblood ABO group in cancer

Rummel

Ellsworth²

2016

Future Sci. OA

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Since the first link between blood type and cancer was described in 1953, numerous studies have sought to determine whether the histoblood ABO group is associated with tumorigenesis. In 2009, the first significant association between a SNP located within the ABO glycosyltransferase gene and increased risk of pancreatic cancer was reported. Here, we describe the history and possible functions of the histoblood ABO group and then provide evidence for a role of blood group antigens in the most common cancer types worldwide using both blood type and SNP data. We also explore whether confusion regarding the role of blood type in cancer risk may be attributable to heterogeneity within tumor types.

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Suppression of FUT1 attenuates cell proliferation in the HER2-overexpressing cancer cell line NCI-N87

Cited by 29 publications

References 28 publications

Fucosylation of LAMP-1 and LAMP-2 by FUT1 correlates with lysosomal positioning and autophagic flux of breast cancer cells

Fucosylation of LAMP-1 and LAMP-2 by FUT1 correlates with lysosomal positioning and autophagic flux of breast cancer cells

MiR-34a suppresses HNSCC growth through modulating cell cycle arrest and senescence

The role of the histoblood ABO group in cancer

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