Fatty acid binding protein 5 promotes metastatic potential of triple negative breast cancer cells through enhancing epidermal growth factor receptor stability.
Fatty acid binding protein 5 promotes metastatic potential of triple negative breast cancer cells through enhancing epidermal growth factor receptor stability.
复制标题
DOI：
10.18632/oncotarget.3442
复制
发表时间：
2015-03-20
期刊：
影响因子：
--
通讯作者：
Ganju RK
中科院分区：
文献类型：
--
作者：
Powell CA;Nasser MW;Zhao H;Wochna JC;Zhang X;Shapiro C;Shilo K;Ganju RK
脂肪酸结合蛋白5（FABP 5）是一种细胞内脂质结合蛋白，已被证明在包括乳腺癌在内的各种癌症中发挥作用。然而，FABP5及其在三阴性乳腺癌（TNBC）中的作用尚未研究。我们在包含423个乳腺癌患者样本的组织微阵列中显示FABP5蛋白表达与TNBC、高级别肿瘤和更差的无病生存相关。在这些样品中，高FABP5表达与表皮生长因子受体（EGFR）表达显著相关。在原位注射小鼠乳腺癌细胞的FABP5 −/−小鼠中观察到肿瘤生长和肺转移减少。TNBC肿瘤细胞中的FABP5损失抑制运动性和侵袭性。机制研究表明，TNBC细胞中的FABP5敲低导致EGFR表达降低，并且FABP5对于EGF诱导的转移信号传导是重要的。FABP5的缺失导致EGFR的蛋白酶体靶向。我们的研究表明，FABP5在乳腺癌进展过程中在宿主和肿瘤细胞中都有作用。这些发现表明，FABP5通过抑制EGFR蛋白酶体降解，部分地通过EGFR介导其对TNBC转移的增强作用。这些研究首次显示了FABP5和EGFR之间通过新机制增强TNBC转移的相关性。
Fatty acid binding protein 5 (FABP5), an intracellular lipid binding protein, has been shown to play a role in various cancers, including breast cancer. However, FABP5 and its role in triple negative breast cancer (TNBC) have not been studied. We show FABP5 protein expression correlates with TNBC, high grade tumors, and worse disease-free survival in a tissue microarray containing 423 breast cancer patient samples. High FABP5 expression significantly correlates with epidermal growth factor receptor (EGFR) expression in these samples. Decreased tumor growth and lung metastasis were observed in FABP5−/− mice othotopically injected with murine breast cancer cells. FABP5 loss in TNBC tumor cells inhibited motility and invasion. Mechanistic studies revealed that FABP5 knockdown in TNBC cells results in decreased EGFR expression and FABP5 is important for EGF-induced metastatic signaling. Loss of FABP5 leads to proteasomal targeting of EGFR. Our studies show that FABP5 has a role in both host and tumor cell during breast cancer progression. These findings suggest that FABP5 mediates its enhanced effect on TNBC metastasis, in part, through EGFR, by inhibiting EGFR proteasomal degradation. These studies show, for the first time, a correlation between FABP5 and EGFR in enhancing TNBC metastasis through a novel mechanism.
登录
查看更多内容
影响因子：
3.3
作者：
Fang, Lei-Ya;Wong, Tung-Yiu;Chen, Yuh-Ling
通讯作者：
Chen, Yuh-Ling
影响因子：
50.5
作者：
Corkery, B.;Crown, J.;O'Donovan, N.
通讯作者：
O'Donovan, N.
影响因子：
4.8
作者：
Kannan-Thulasiraman, Padmamalini;Seachrist, Darcie D.;Noy, Noa
通讯作者：
Noy, Noa
影响因子：
3.8
作者：
Masuda, Hiroko;Zhang, Dongwei;Bartholomeusz, Chandra;Doihara, Hiroyoshi;Hortobagyi, Gabriel N.;Ueno, Naoto T.
通讯作者：
Ueno, Naoto T.
影响因子：
7.7
作者：
Maeda, K;Uysal, KT;Hotamisligil, GS
通讯作者：
Hotamisligil, GS