A novel role for flotillin‐1 in H‐Ras‐regulated breast cancer aggressiveness

Elevated expression and aberrant activation of Ras have been implicated in breast cancer aggressiveness. H‐Ras, but not N‐Ras, induces breast cell invasion. A crucial link between lipid rafts and H‐Ras function has been suggested. This study sought to identify the lipid raft protein(s) responsible f...

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Veröffentlicht in:International journal of cancer 2016-03, Vol.138 (5), p.1232-1245
Hauptverfasser: Koh, Minsoo, Yong, Hae‐Young, Kim, Eun‐Sook, Son, Hwajin, Jeon, You Rim, Hwang, Jin‐Sun, Kim, Myeong‐Ok, Cha, Yujin, Choi, Wahn Soo, Noh, Dong‐Young, Lee, Kyung‐Min, Kim, Ki‐Bum, Lee, Jae‐Seon, Kim, Hyung Joon, Kim, Haemin, Kim, Hong‐Hee, Kim, Eun Joo, Park, So Yeon, Kim, Hoe Suk, Moon, Woo Kyung, Choi Kim, Hyeong‐Reh, Moon, Aree
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Sprache:eng
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Zusammenfassung:Elevated expression and aberrant activation of Ras have been implicated in breast cancer aggressiveness. H‐Ras, but not N‐Ras, induces breast cell invasion. A crucial link between lipid rafts and H‐Ras function has been suggested. This study sought to identify the lipid raft protein(s) responsible for H‐Ras‐induced tumorigenicity and invasiveness of breast cancer. We conducted a comparative proteomic analysis of lipid raft proteins from invasive MCF10A human breast epithelial cells engineered to express active H‐Ras and non‐invasive cells expressing active N‐Ras. Here, we identified a lipid raft protein flotillin‐1 as an important regulator of H‐Ras activation and breast cell invasion. Flotillin‐1 was required for epidermal growth factor‐induced activation of H‐Ras, but not that of N‐Ras, in MDA‐MB‐231 triple‐negative breast cancer (TNBC) cells. Flotillin‐1 knockdown inhibited the invasiveness of MDA‐MB‐231 and Hs578T TNBC cells in vitro and in vivo. In xenograft mouse tumor models of these TNBC cell lines, we showed that flotillin‐1 played a critical role in tumor growth. Using human breast cancer samples, we provided clinical evidence for the metastatic potential of flotillin‐1. Membrane staining of flotillin‐1 was positively correlated with metastatic spread (p = 0.013) and inversely correlated with patient disease‐free survival rates (p = 0.005). Expression of flotillin‐1 was associated with H‐Ras in breast cancer, especially in TNBC (p 
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.29869