Tumour suppressor gene function in carcinoma-associated fibroblasts: from tumour cells via EMT and back again?
Tumour suppressor gene function in carcinoma-associated fibroblasts: from tumour cells via EMT and back again?
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DOI：
10.1002/path.4298
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发表时间：
2014-03
期刊：
影响因子：
--
通讯作者：
Macleod KF
中科院分区：
文献类型：
--
作者：
Drake LE;Macleod KF
近期报道表明，在口咽癌、乳腺癌和其他人类癌症的肿瘤间质中检测到RB、TP53或PTEN肿瘤抑制基因失活。小鼠模型已证实，在成纤维细胞中删除Rb、Pten或p53具有促肿瘤作用，可将其从正常成纤维细胞转化为癌相关成纤维细胞（CAFs）。在这些情况下，CAFs的促肿瘤活性与CAFs产生特定生长因子、趋化因子和基质金属蛋白酶（MMPs）从而增加对肿瘤细胞的旁分泌信号传导有关。正常成纤维细胞（NOFs）通过获得特定突变（如肿瘤抑制因子缺失），或微小RNA表达失调或关键表观遗传事件而转化为CAFs，这显然可以独立于肿瘤细胞的遗传和表观遗传变化发生，但目前正在重新考虑的CAFs的另一个来源是，CAFs通过上皮 - 间质转化（EMT）来源于肿瘤细胞。近期采用谱系追踪技术的小鼠模型表明，这种情况可在体内发生，并对其更广泛的相关性程度进行了讨论。
Recent reports indicate that inactivation of the RB, TP53 or PTEN tumour suppressor genes is detected in tumour stroma of oropharyngeal, breast and other human cancers. Mouse models have validated the tumour-promoting effects of deleting Rb, Pten or p53 in fibroblasts that converts them from normal fibroblasts to carcinoma associated fibroblasts (CAFs). The tumour-promoting activity of CAFs in these contexts was associated with increased paracrine signaling to tumour cells through production of specific growth factors, chemokines and MMPs by CAFs. The conversion of NOFs into CAFs through acquisition of specific mutations, such as loss of tumour suppressors, or deregulated expression of microRNAs or key epigenetic events, can clearly occur independently of genetic and epigenetic changes in tumour cells but an alternative source of CAFs that is being reconsidered is that CAFs derive from the tumour cells by EMT. Recent mouse models employing lineage-tracing techniques have suggested that this can take place in vivo and the extent to which this is relevant more broadly is discussed.
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影响因子：
--
作者：
Cichon AC;Pickard A;McDade SS;Sharpe DJ;Moran M;James JA;McCance DJ
通讯作者：
McCance DJ
影响因子：
50.3
作者：
Hanahan, Douglas;Coussens, Lisa M.
通讯作者：
Coussens, Lisa M.
DOI：
10.1073/pnas.0401064101
发表时间：
2004-04-06
影响因子：
11.1
作者：
Kuperwasser, C;Chavarria, T;Weinberg, RA
通讯作者：
Weinberg, RA
DOI：
10.1073/pnas.211053698
发表时间：
2001-10-09
影响因子：
11.1
作者：
Krtolica, A;Parrinello, S;Campisi, J
通讯作者：
Campisi, J
影响因子：
50.3
作者：
Guerra C;Collado M;Navas C;Schuhmacher AJ;Hernández-Porras I;Cañamero M;Rodriguez-Justo M;Serrano M;Barbacid M
通讯作者：
Barbacid M