Is dysfunction of caveolin-1 a link between systemic sclerosis and breast cancer, opening a window on both etiologies?
Epidemiological and institutional studies have demonstrated an association between systemic sclerosis (SSc) and breast cancer. For example, breast cancer is one of the most common cancers seen in SSc patients, whereas a higher rate of cutaneous scleroderma appeared in a group in which SSc followed breast cancer diagnosis. Additionally, sex hormones and genetic factors within the estrogen receptor (ER) influence the development of SSc and breast cancer. An older age at diagnosis of SSc, lack of antinuclear antibody positivity and the presence of pulmonary fibrosis are shown to be associated with the development of breast cancer in SSc patients. On the other hand, increased mammographic densities that may be caused by SSc are an important risk factor for breast cancer development. Despite the evidence that SSc and breast cancer are epidemiologically linked, the cause of this correlation is unclear. Caveolin-1 (Cav-1) is a negative regulator that inhibits the basal activity of several pro-proliferative and oncogenic proteins. Cav-1 regulated TGF-beta/Smad signaling appears to participate in the pathogenesis of breast cancer and tissue fibrosis in SSc. Thus, it is proposed that Cav-1 regulated TGF-beta/Smad signaling via Cav-1 scaffolding domain (CSD) may play a key role in the link between SSc and breast cancer by suppressing TGF-beta-mediated phosphorylation of Smad. Future studies of Cav-1 regulated TGF-beta/Smad signaling may lead to novel insights into the link between SSc and breast cancer and may also lead to new strategies for the management of these two fatal diseases.
Qian
Niansong
N
Department of Breast Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Ueno
Takayuki
T
D001943:Breast Neoplasms / Q000209:etiology* / Q000503:physiopathology; D051242:Caveolin 1 / Q000502:physiology*; D005260:Female; D006801:Humans; D012595:Scleroderma, Systemic / Q000209:etiology* / Q000503:physiopathology
D051242:Caveolin 1