JG6, a novel marine-derived oligosaccharide, suppresses breast cancer metastasis via binding to cofilin

Huang, Xun; Sun, Danni; Pan, Qiuming; Wen, Weiwei; Chen, Yi; Xin, Xianliang; Huang, Min; Ding, Jian; Geng, Meiyu

doi:10.18632/oncotarget.1959

Cited by 15 publications

(9 citation statements)

References 36 publications

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“…Significant future work will be needed to test this hypothesis and validate the functionality of DSLS in vivo. Given numerous gap junction-inhibitors and the discovery of cofilin-binding oligosaccharide JG6, itself shown to be capable of suppressing lung metastasis in mice, there may be a future translation of this data to the prevention or suppression of bone metastasis 40,41 . We realize that morphological evidence may not be sufficient to support the uniqueness of DSLSit might indeed be molecularly related to one of these previously described structures.…”

Section: Discussionmentioning

confidence: 99%

Unique cellular protrusions mediate breast cancer cell migration by tethering to osteogenic cells

et al. 2020

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Migration and invasion are key properties of metastatic cancer cells. These properties can be acquired through intrinsic reprogramming processes such as epithelial-mesenchymal transition. In this study, we discovered an alternative “migration-by-tethering” mechanism through which cancer cells gain the momentum to migrate by adhering to mesenchymal stem cells or osteoblasts. This tethering is mediated by both heterotypic adherens junctions and gap junctions, and leads to a unique cellular protrusion supported by cofilin-coated actin filaments. Inhibition of gap junctions or depletion of cofilin reduces migration-by-tethering. We observed evidence of these protrusions in bone segments harboring experimental and spontaneous bone metastasis in animal models. These data exemplify how cancer cells may acquire migratory ability without intrinsic reprogramming. Furthermore, given the important roles of osteogenic cells in early-stage bone colonization, our observations raise the possibility that migration-by-tethering may drive the relocation of disseminated tumor cells between different niches in the bone microenvironment.

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Section: Discussionmentioning

confidence: 99%

Unique cellular protrusions mediate breast cancer cell migration by tethering to osteogenic cells

et al. 2020

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“…In migrating or invading cells, cofilin resides in cell membrane protrusions, for example lamellipodia, invadopodia, and filopodia, which initiate cell movement and determine cell polarity ( 36 , 37 ). This localization is critical for cell movement, endocytosis and cell division, all of which are important for normal cell proliferation, differentiation and cancer development ( 38 ). This promotion may be responsible for the positive association between cofilin expression and NHG, Her2 and Ki-67 status.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of cofilin correlates with poor survival in breast cancer: A tissue microarray analysis

et al. 2017

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Cofilin, a key regulator of actin cytoskeleton dynamics, is considered to be involved in cellular migration, tumor invasion and mitosis, and its activity is increased in cancer cells. To address the association between cofilin and breast cancer prognosis, which is unclear at present, cofilin expression was analyzed in tissue microarrays of tumors from 310 patients with breast cancer via immunohistochemistry. In a multivariate Cox regression analysis, a high expression of cofilin in tumor cells correlated significantly with shorter overall survival (hazard ratio, 2.22; 95% confidence interval, 1.35–3.66, P=0.002, and with the Nottingham histologic grade, Ki-67 status and human epidermal growth factor receptor 2 status (P=0.031, 0.001, and 0.001, respectively). Cofilin expression was not observed as correlated with estrogen or progesterone receptor expression, tumor size or lymph node status. These data demonstrate that cofilin is associated with poor outcome, thereby suggesting that it is a potential prognostic factor in breast cancer.

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“…It has been demonstrated that cofilin promotes invadopodial membrane recycling during cell invasion (11). Moreover, cofilin has been demonstrated to act as a key regulator in cancer cell motility (26,27). For instance, Chen et al (28) showed that cofilin was a critical signaling pathway involved in miR-138-mediated ovarian cancer cell metastasis.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-429 inhibits the migration and invasion of colon cancer cells by targeting PAK6/cofilin signaling

et al. 2015

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MicroRNAs (miRs), a class of non-coding RNAs 18-25 nucleotides in length, can lead to mRNA degradation or inhibit protein translation by directly binding to the 3'-untranslational region (UTR) of their target mRNAs. The deregulation of miR-429 has been suggested to be involved in the development and progression of colon cancer. However, the detailed molecular mechanism involved remains to be determined. The aim of the present study was to investigate the role of miR-429 in the regulation of migration and invasion of colon cancer cells using RT-qPCR and western blotting. The results showed that the expression of miR-429 was reduced in colon cancer cell lines, when compared to a normal colon epithelial cell line. Treatment with DNA demethylation agent 5-aza-2'-deoxycytidine and histone deacetylase inhibitor phenylbutyrate (PBA), or transfection with the pre-miR-429 lentivirus plasmid led to the upregulation of miR-429 expression, as well as inhibition of migration and invasion in colon cancer cells. Investigation of the molecular mechanism showed that PAK6 was a novel target of miR-429, and the expression of PAK6 was upregulated in colon cancer tissues and cell lines, and was negatively regulated by miR-429 in colon cancer cells. Moreover, the cofilin signaling acted as a downstream effector of miR-429 in colon cancer cells. In conclusion, the results of the present study suggested that miR-429 inhibits the migration and invasion of colon cancer cells, partly at least, by mediating the expression of PAK6, as well as the activity of cofilin signaling. Therefore, miR-429 is as a potential molecular target for the treatment of colon cancer.

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JG6, a novel marine-derived oligosaccharide, suppresses breast cancer metastasis via binding to cofilin

Cited by 15 publications

References 36 publications

Unique cellular protrusions mediate breast cancer cell migration by tethering to osteogenic cells

Unique cellular protrusions mediate breast cancer cell migration by tethering to osteogenic cells

Overexpression of cofilin correlates with poor survival in breast cancer: A tissue microarray analysis

MicroRNA-429 inhibits the migration and invasion of colon cancer cells by targeting PAK6/cofilin signaling

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