Structural determinant of BST-2-mediated regulation of breast cancer cell motility: a role for cytoplasmic tail tyrosine residues

Naushad, Wasifa; Mahauad‐Fernandez, Wadie D.; Okeoma, Chioma M.

doi:10.18632/oncotarget.22753

Cited by 7 publications

(11 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Expression of BST-2 is regulated by both extrinsic and intrinsic stimuli, including cytokines such as interferons 20 , 23 , 24 . In different disease conditions, such as autoimmune diseases 25 , 26 and different malignancies, BST-2 has been reported to be overexpressed 5 , 27 , 28 . BST-2 DNA is hypomethylated in breast cancer cells leading to its overexpression 3 .…”

Section: Introductionmentioning

confidence: 99%

BST-2 promotes survival in circulation and pulmonary metastatic seeding of breast cancer cells

Mahauad‐Fernandez

Naushad

Panzner

et al. 2018

Sci Rep

Self Cite

View full text Add to dashboard Cite

Bone marrow stromal antigen 2 (BST-2) mediates various facets of cancer progression and metastasis. Here, we show that BST-2 is linked to poor survival in invasive breast cancer patients as its expression positively correlates with disease severity. However, the mechanisms that drive the pro‐metastatic functions of BST-2 are not fully understood. Correlation of BST-2 expression and tumor aggressiveness was analyzed in human tissue samples. Migration, invasion, and competitive experimental metastasis assays were used to measure the cellular responses after silencing BST-2 expression. Using a mouse model of breast cancer, we show that BST-2 promotes metastasis independent of the primary tumor. Additional experiments show that suppression of BST-2 renders non-adherent cancer cells non-viable by sensitizing cells to anoikis. Embedment of cancer cells in basement membrane matrix reveals that silencing BTS-2 expression inhibits invadopodia formation, extracellular matrix degradation, and subsequent cell invasion. Competitive experimental pulmonary metastasis shows that silencing BST-2 reduces the numbers of viable circulating tumor cells (CTCs) and decreases the efficiency of lung colonization. Our data define a previously unknown function for BST-2 in the i) formation of invadopodia, ii) degradation of extracellular matrix, and iii) protection of CTCs from hemodynamic stress. We believe that physical (tractional forces) and biochemical (ECM type/composition) cues may control BST-2’s role in cell survival and invadopodia formation. Collectively, our findings highlight BST-2 as a key factor that allows cancer cells to invade, survive in circulation, and at the metastatic site.

show abstract

Section: Introductionmentioning

confidence: 99%

BST-2 promotes survival in circulation and pulmonary metastatic seeding of breast cancer cells

Mahauad‐Fernandez

Naushad

Panzner

et al. 2018

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Of note, the growth inhibition was absent in MDA-MB 231 cells in which BST-2 expression has been suppressed (Fig. 6D ) with BST-2-targeting shRNA 23 . These results show that even in 3D-embedment culture conditions, B49Mod1 inhibits cancer cell growth in a BST-2-dependent manner.…”

Section: Resultsmentioning

confidence: 93%

B49, a BST-2-based peptide, inhibits adhesion and growth of breast cancer cells

Mahauad‐Fernandez

Okeoma

2018

Sci Rep

Self Cite

View full text Add to dashboard Cite

Bone marrow stromal antigen 2 (BST-2) also known as Tetherin has been implicated in the growth and progression of many cancers. BST-2 employs its pro-tumor effects through the formation of BST-2:BST-2 dimers which ultimately promotes cell to cell and cell to matrix adhesion, cell motility, survival, and growth. The aim of this study was to evaluate the effect of a novel BST-2-based peptide—B49 on adhesion and growth of breast cancer cells. Homotypic/heterotypic adhesion, three-dimensional spheroid formation, and anchorage-independent growth were used to assess the effect of B49 on cell adhesion and growth. Additionally, we provide evidence of the anti-tumor effect of B49 in a preclinical mouse model of breast cancer. Results show that breast cancer cell adhesion to other cancer cells or components of the tumor microenvironment were inhibited by B49. Most well-known evaluation indexes of cancer cell growth, including spheroid formation, anchorage-independent, and primary tumor growth were significantly inhibited by B49. These data affirm that i) BST-2 plays a key role in mediating breast cancer cell adhesion and growth, and ii) B49 and its analog B49Mod1 significantly inhibits BST-2-mediated cancer cell adhesion and growth. Therefore, B49 and its analogs offer a promising anti-adhesion and therapeutic lead for BST-2-dependent cancers.

show abstract

“…Findings from many labs have shown that BST-2 is overexpressed in several cancers including lung cancer [17], head and neck carcinomas [18], oral cavity cancers [19], glioblastomas [20], endometrial cancer [21], lymphomas [22], and breast cancer [23,24]. In breast cancer cells, elevated levels of BST-2 have been associated with increased cancer cell migration [24][25][26], invasion [24,26,27], adhesion, and resistance to apoptosis/anoikis [28,29]. In addition, it has been suggested that increased immune cell adhesion and resistance of cancer cells to tamoxifen-induced apoptosis is linked to BST-2 expression [27,28,30].…”

Section: Introductionmentioning

confidence: 99%

Development and Characterization of the Shortest Anti-Adhesion Peptide Analogue of B49Mod1

2020

Self Cite

View full text Add to dashboard Cite

Inhibition of cancer cell adhesion is an effective approach to killing adherent cancer cells. B49 and its analog B49Mod1 peptides, derived from the extracellular domain (ECD) of bone marrow stromal antigen 2 (BST-2), display anti-adhesion activity on breast cancer cells. However, the minimal sequence required for this anti-adhesion activity is unknown. Here, we further characterized the anti-adhesion activity of B49Mod1. We show that the anti-adhesion activity of B49Mod1 may require cysteine-linked disulfide bond and that the peptide is susceptible to proteolytic deactivation. Using structure-activity relationship studies, we identified an 18-Mer sequence (B18) as the minimal peptide sequence mediating the anti-adhesion activity of B49Mod1. Atomistic molecular dynamic (MD) simulations reveal that B18 forms a stable complex with the ECD of BST-2 in aqueous solution. MD simulations further reveal that B18 may cause membrane defects that facilitates peptide translocation across the bilayer. Placement of four B18 chains as a transmembrane bundle results in water channel formation, indicating that B18 may impair membrane integrity and form pores. We hereby identify B18 as the minimal peptide sequence required for the anti-adhesion activity of B49Mod1 and provide atomistic insight into the interaction of B18 with BST-2 and the cell membrane.

show abstract

Structural determinant of BST-2-mediated regulation of breast cancer cell motility: a role for cytoplasmic tail tyrosine residues

Cited by 7 publications

References 48 publications

BST-2 promotes survival in circulation and pulmonary metastatic seeding of breast cancer cells

BST-2 promotes survival in circulation and pulmonary metastatic seeding of breast cancer cells

B49, a BST-2-based peptide, inhibits adhesion and growth of breast cancer cells

Development and Characterization of the Shortest Anti-Adhesion Peptide Analogue of B49Mod1

Contact Info

Product

Resources

About