mLST8 Promotes mTOR-Mediated Tumor Progression.
mLST8 Promotes mTOR-Mediated Tumor Progression.
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DOI：
10.1371/journal.pone.0119015
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Oneyama C
中科院分区：
文献类型：
--
作者：
Kakumoto K;Ikeda J;Okada M;Morii E;Oneyama C
雷帕霉素（mTOR）的机制靶点的活性在各种类型的人类癌症中升高，暗示在肿瘤进展中的作用。然而，mTOR上调的分子机制仍不清楚。在这项研究中，我们发现mLST 8的表达，mTOR复合物1（mTORC 1）和复合物2（mTORC 2）所需的亚基，在几个人结肠癌和前列腺癌细胞系和组织中上调。mLST 8的敲除显著抑制mTORC 1和mTORC 2复合物的形成，并且它还抑制人结肠癌（HCT 116）和前列腺癌（LNCaP）细胞中的肿瘤生长和侵袭。mLST 8的过表达诱导正常上皮细胞（HaCaT）中的锚定非依赖性细胞生长，尽管mLST 8敲低对正常细胞生长没有影响。mLST 8敲低降低了癌细胞和正常细胞中mTORC 2介导的AKT磷酸化，而它有效地抑制了癌细胞中mTORC 1介导的4 E-BP 1磷酸化。这些结果表明，mLST 8在正常细胞和癌细胞中起着不同的作用，这取决于其表达水平，mLST 8上调可能有助于肿瘤的进展，通过组成性激活mTORC 1和mTORC 2途径。
The activity of the mechanistic target of rapamycin (mTOR) is elevated in various types of human cancers, implicating a role in tumor progression. However, the molecular mechanisms underlying mTOR upregulation remain unclear. In this study, we found that the expression of mLST8, a required subunit of both mTOR complex 1 (mTORC1) and complex 2 (mTORC2), was upregulated in several human colon and prostate cancer cell lines and tissues. Knockdown of mLST8 significantly suppressed mTORC1 and mTORC2 complex formation, and it also inhibited tumor growth and invasiveness in human colon carcinoma (HCT116) and prostate cancer (LNCaP) cells. Overexpression of mLST8 induced anchorage-independent cell growth in normal epithelial cells (HaCaT), although mLST8 knockdown had no effect on normal cell growth. mLST8 knockdown reduced mTORC2-mediated phosphorylation of AKT in both cancer and normal cells, whereas it potently inhibited mTORC1-mediated phosphorylation of 4E-BP1 specifically in cancer cells. These results suggest that mLST8 plays distinct roles in normal and cancer cells, depending upon its expression level, and that mLST8 upregulation may contribute to tumor progression by constitutively activating both the mTORC1 and mTORC2 pathways.
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影响因子：
3.7
作者：
Oneyama C;Kito Y;Asai R;Ikeda J;Yoshida T;Okuzaki D;Kokuda R;Kakumoto K;Takayama K;Inoue S;Morii E;Okada M
通讯作者：
Okada M
影响因子：
11
作者：
Nakashima A;Kawanishi I;Eguchi S;Yu EH;Eguchi S;Oshiro N;Yoshino K;Kikkawa U;Yonezawa K
通讯作者：
Yonezawa K
影响因子：
--
作者：
Nagaraja, Ankur K.;Creighton, Chad J.;Matzuk, Martin M.
通讯作者：
Matzuk, Martin M.
影响因子：
16
作者：
Kim, DH;Sarbassov, DD;Sabatini, DM
通讯作者：
Sabatini, DM
影响因子：
7.3
作者：
Guertin, David A.;Sabatini, David M.
通讯作者：
Sabatini, David M.