Abstract
Understanding what drives breast tumor progression is of utmost importance for blocking tumor metastasis; we have identified that semaphorin 7a is a potent driver of ductal carcinoma in situ (DCIS) progression. Semaphorin 7a is a glycophosphatidylinositol membrane-anchored protein that promotes attachment and spreading in multiple cell types. Here, we show that increased expression of SEMA7A occurs in a large percentage of breast cancers and is associated with decreased overall and distant metastasis-free survival. In both in vitro and in vivo models, short hairpin-mediated silencing of SEMA7A reveals roles for semaphorin 7a in the promotion of DCIS growth, motility and invasion as well as lymphangiogenesis in the tumor microenvironment. Our studies also uncover a relationship between COX-2 and semaphorin 7a expression and suggest that semaphorin 7a promotes tumor cell invasion on collagen and lymphangiogenesis via activation of β 1 -integrin receptor. Our results suggest that semaphorin 7a may be novel target for blocking breast tumor progression.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 5170-5178 |
| Number of pages | 9 |
| Journal | Oncogene |
| Volume | 35 |
| Issue number | 39 |
| DOIs | |
| State | Published - Sep 29 2016 |
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ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research
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Semaphorin 7a exerts pleiotropic effects to promote breast tumor progression. / Black, S. A.; Nelson, A. C.; Gurule, N. J.; Futscher, Bernard W; Lyons, T. R.
In: Oncogene, Vol. 35, No. 39, 29.09.2016, p. 5170-5178.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Semaphorin 7a exerts pleiotropic effects to promote breast tumor progression
AU - Black, S. A.
AU - Nelson, A. C.
AU - Gurule, N. J.
AU - Futscher, Bernard W
AU - Lyons, T. R.
PY - 2016/9/29
Y1 - 2016/9/29
N2 - Understanding what drives breast tumor progression is of utmost importance for blocking tumor metastasis; we have identified that semaphorin 7a is a potent driver of ductal carcinoma in situ (DCIS) progression. Semaphorin 7a is a glycophosphatidylinositol membrane-anchored protein that promotes attachment and spreading in multiple cell types. Here, we show that increased expression of SEMA7A occurs in a large percentage of breast cancers and is associated with decreased overall and distant metastasis-free survival. In both in vitro and in vivo models, short hairpin-mediated silencing of SEMA7A reveals roles for semaphorin 7a in the promotion of DCIS growth, motility and invasion as well as lymphangiogenesis in the tumor microenvironment. Our studies also uncover a relationship between COX-2 and semaphorin 7a expression and suggest that semaphorin 7a promotes tumor cell invasion on collagen and lymphangiogenesis via activation of β 1 -integrin receptor. Our results suggest that semaphorin 7a may be novel target for blocking breast tumor progression.
AB - Understanding what drives breast tumor progression is of utmost importance for blocking tumor metastasis; we have identified that semaphorin 7a is a potent driver of ductal carcinoma in situ (DCIS) progression. Semaphorin 7a is a glycophosphatidylinositol membrane-anchored protein that promotes attachment and spreading in multiple cell types. Here, we show that increased expression of SEMA7A occurs in a large percentage of breast cancers and is associated with decreased overall and distant metastasis-free survival. In both in vitro and in vivo models, short hairpin-mediated silencing of SEMA7A reveals roles for semaphorin 7a in the promotion of DCIS growth, motility and invasion as well as lymphangiogenesis in the tumor microenvironment. Our studies also uncover a relationship between COX-2 and semaphorin 7a expression and suggest that semaphorin 7a promotes tumor cell invasion on collagen and lymphangiogenesis via activation of β 1 -integrin receptor. Our results suggest that semaphorin 7a may be novel target for blocking breast tumor progression.
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U2 - 10.1038/onc.2016.49
DO - 10.1038/onc.2016.49
M3 - Article
VL - 35
SP - 5170
EP - 5178
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 39
ER -