The G12 family of heterotrimeric G proteins promotes breast cancer invasion and metastasis.
Although the prognosis for patients with early-stage breast cancer has improved, the therapeutic options for patients with locally advanced and metastatic disease are limited. To improve the treatment of these patients, the molecular mechanisms underlying breast cancer invasion and metastasis must be understood. In this study, we report that signaling through the G12 family of heterotrimeric G proteins (Galpha12 and Galpha13) promotes breast cancer cell invasion. Moreover, we demonstrate that inhibition of G12 signaling reduces the metastatic dissemination of breast cancer cells in vivo. Finally, we demonstrate that the expression of Galpha12 is significantly up-regulated in the earliest stages of breast cancer, implying that amplification of G12 signaling may be an early event in breast cancer progression. Taken together, these observations identify the G12 family proteins as important regulators of breast cancer invasion and suggest that these proteins may be targeted to limit invasion- and metastasis-induced patient morbidity and mortality.
Kelly
Patrick
P
Department Pharmacology, Duke University Medical Center, Durham, NC 27710, USA.
Moeller
Benjamin J
BJ
Juneja
Juhi
J
Booden
Michelle A
MA
Der
Channing J
CJ
Daaka
Yehia
Y
Dewhirst
Mark W
MW
Fields
Timothy A
TA
Casey
Patrick J
PJ
D000230:Adenocarcinoma / Q000378:metabolism; D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000737:chemistry / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D012190:Retroviridae / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
D015820:Cadherins; D044365:GTP-Binding Protein alpha Subunits, G12-G13