Ectopically expressed variant form of sperm mitochondria-associated cysteine-rich protein augments tumorigenicity of the stem cell population of lung adenocarcinoma cells.
Ectopically expressed variant form of sperm mitochondria-associated cysteine-rich protein augments tumorigenicity of the stem cell population of lung adenocarcinoma cells.
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DOI：
10.1371/journal.pone.0069095
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sato N
中科院分区：
文献类型：
--
作者：
Takahashi A;Hirohashi Y;Torigoe T;Tamura Y;Tsukahara T;Kanaseki T;Kochin V;Saijo H;Kubo T;Nakatsugawa M;Asanuma H;Hasegawa T;Kondo T;Sato N
癌症干细胞样细胞（cancer stem-like cells，CSC）/癌症起始细胞（cancer-initiating cells，CIC）是指具有自我更新能力、分化能力和高肿瘤起始能力的小群体癌细胞。CSC/CIC对癌症疗法（包括化学疗法和放射疗法）具有抗性。因此，CSC/CIC被认为是治疗后癌症复发和远处转移的原因。然而，CSC/CIC的分子机制仍然是难以捉摸的。本研究从肺癌、结肠癌和乳腺癌细胞中分离CSCs/CIC作为侧群（side population，SP）细胞，并分析CSCs/CIC的分子机制。cDNA微阵列筛选和RT-PCR分析表明，精子相关的富含半胱氨酸蛋白（SMCP）在SP细胞异位表达。5′-cDNA末端快速扩增（RACE）分析表明，SMCP在SP细胞中的转录本是由一个外显子组成的变异体（vt 2）。SMCP vt 2仅在癌细胞中检测到，而野生型（vt 1）形式的SMCP在睾丸中表达。SMCP在肺癌细胞中通过SMCP过表达和使用siRNA敲低SMCP而显示出在肿瘤起始中具有作用。综上所述，启动结果表明，SMCP的异位表达的变体形式在CSC/CIC的肿瘤启动中具有作用，并且SMCP的变体形式可能是一种新的CSC/CIC标记物，并且是CSC/CIC靶向治疗的潜在和有希望的靶点。
Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as a small population of cancer cells that have self-renewal ability, differentiation ability and high tumor-initiating ability. CSCs/CICs are resistant to cancer therapies including chemotherapy and radiotherapy. Therefore, CSCs/CICs are thought to be responsible for cancer recurrence and distant metastasis after treatment. However, the molecular mechanisms of CSCs/CICs are still elusive. In this study, we isolated CSCs/CICs as side population (SP) cells from lung carcinoma, colon carcinoma and breast carcinoma cells and analyzed the molecular mechanisms of CSCs/CICs. cDNA micro-array screening and RT-PCR analysis revealed that sperm mitochondria-associated cysteine-rich protein (SMCP) is ectopically expressed in SP cells. 5′-Rapid amplification of cDNA end (RACE) analysis revealed that the SMCP transcript in SP cells was a variant form (termed vt2) which is composed from only one exon. SMCP vt2 was detected in only cancer cells, whereas the wild-type (vt1) form of SMCP was expressed in the testis. SMCP was shown to have a role in tumor initiation by SMCP overexpression and SMCP knockdown using siRNAs in lung cancer cells. Taken together, the initiation results indicate that an ectopically expressed variant form of SMCP has a role in tumor initiation of CSCs/CICs and that the variant form of SMCP might be a novel CSC/CIC marker and a potential and promising target of CSC/CIC-targeting therapy.
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影响因子：
7.3
作者：
Burkert, J.;Otto, W. R.;Wright, N. A.
通讯作者：
Wright, N. A.
影响因子：
4.4
作者：
Aho, H;Schwemmer, M;Adham, IM
通讯作者：
Adham, IM
影响因子：
12.4
作者：
Eramo, A.;Lotti, F.;De Maria, R.
通讯作者：
De Maria, R.
DOI：
10.1073/pnas.0703478104
发表时间：
2007-06-12
影响因子：
11.1
作者：
Dalerba, Piero;Dylla, Scott J.;Clarke, Michael F.
通讯作者：
Clarke, Michael F.
影响因子：
11.2
作者：
Collins, AT;Berry, PA;Maitland, NJ
通讯作者：
Maitland, NJ