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A microRNA code for prostate cancer metastasis
#MMPMID26073083
Bonci D
; Coppola V
; Patrizii M
; Addario A
; Cannistraci A
; Francescangeli F
; Pecci R
; Muto G
; Collura D
; Bedini R
; Zeuner A
; Valtieri M
; Sentinelli S
; Benassi MS
; Gallucci M
; Carlini P
; Piccolo S
; De Maria R
Oncogene
2016[Mar]; 35
(9
): 1180-92
PMID26073083
show ga
Although the development of bone metastasis is a major detrimental event in
prostate cancer, the molecular mechanisms responsible for bone homing and
destruction remain largely unknown. Here we show that loss of miR-15 and miR-16
in cooperation with increased miR-21 expression promote prostate cancer spreading
and bone lesions. This combination of microRNA endows bone-metastatic potential
to prostate cancer cells. Concomitant loss of miR-15/miR-16 and gain of miR-21
aberrantly activate TGF-? and Hedgehog signaling, that mediate local invasion,
distant bone marrow colonization and osteolysis by prostate cancer cells. These
findings establish a new molecular circuitry for prostate cancer metastasis that
was validated in patients' cohorts. Our data indicate a network of biomarkers and
druggable pathways to improve patient treatment.
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