HOXB9, a gene overexpressed in breast cancer, promotes tumorigenicity and lung metastasis.
The mechanisms underlying tumoral secretion of signaling molecules into the microenvironment, which modulates tumor cell fate, angiogenesis, invasion, and metastasis, are not well understood. Aberrant expression of transcription factors, which has been implicated in the tumorigenesis of several types of cancers, may provide a mechanism that induces the expression of growth and angiogenic factors in tumors, leading to their local increase in the tumor microenvironment, favoring tumor progression. In this report, we demonstrate that the transcription factor HOXB9 is overexpressed in breast carcinoma, where elevated expression correlates with high tumor grade. HOXB9 induces the expression of several angiogenic factors (VEGF, bFGF, IL-8, and ANGPTL-2), as well as ErbB (amphiregulin, epiregulin, and neuregulins) and TGF-ss, which activate their respective pathways, leading to increased cell motility and acquisition of mesenchymal phenotypes. In vivo, HOXB9 promotes the formation of large, well-vascularized tumors that metastasize to the lung. Thus, deregulated expression of HOXB9 contributes to breast cancer progression and lung metastasis by inducing several growth factors that alter tumor-specific cell fates and the tumor stromal microenvironment.
Hayashida
Tetsu
T
Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Takahashi
Fumiyuki
F
Chiba
Naokazu
N
Brachtel
Elena
E
Takahashi
Motomi
M
Godin-Heymann
Nadia
N
Gross
Kenneth W
KW
Vivanco
Maria d M
Md
Wijendran
Vasuki
V
Shioda
Toshihiro
T
Sgroi
Dennis
D
Donahoe
Patricia K
PK
Maheswaran
Shyamala
S
D001943:Breast Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary*; D009389:Neovascularization, Pathologic
C491257:HOXB9 protein, human; D018398:Homeodomain Proteins