Deregulation of the CEACAM expression pattern causes undifferentiated cell growth in human lung adenocarcinoma cells.
Deregulation of the CEACAM expression pattern causes undifferentiated cell growth in human lung adenocarcinoma cells.
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CEACAM表达模式的放松管制会导致人肺腺癌细胞中未分化的细胞生长。
DOI：
10.1371/journal.pone.0008747
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发表时间：
2010-01-18
期刊：
影响因子：
3.7
通讯作者：
Slevogt H
中科院分区：
文献类型：
--
作者：
Singer BB;Scheffrahn I;Kammerer R;Suttorp N;Ergun S;Slevogt H
CEACAM 1、CEA/CEACAM 5和CEACAM 6是癌胚抗原（CEA）家族的细胞粘附分子（CAM），其已显示在肺癌和高达50%的所有人类癌症中失调。然而，关于这些分子对未分化细胞生长和肿瘤进展的功能影响知之甚少。在这里，我们证明了细胞表面表达CEACAM 1融合A549人肺腺癌细胞在分化，接触抑制细胞生长中起着关键作用。有趣的是，CEACAM 1-L，而不是CEACAM 1-S，通过其ITIM结构域负调控增殖，而在增殖细胞中没有检测到CEACAM表达。此外，我们首次表明CEACAM 6在A549细胞中作为细胞增殖的诱导剂，可能通过干扰CEACAM 1 -4L触发的接触抑制信号，导致未分化的锚定非依赖性细胞生长。我们还发现，A549细胞表达大量的CEACAM 5和CEACAM 6的非膜锚定变体，这代表了肺癌患者中常见的CEACAM 5/6血清水平升高的假定来源。综上所述，我们的数据表明，融合后的接触抑制是建立和维持CEACAM 1 -4L，但CEACAM 1 -4S和其他CEACAMs的CEACAM 1信号的干扰导致未分化的细胞生长和恶性转化。
CEACAM1, CEA/CEACAM5, and CEACAM6 are cell adhesion molecules (CAMs) of the carcinoembryonic antigen (CEA) family that have been shown to be deregulated in lung cancer and in up to 50% of all human cancers. However, little is known about the functional impact of these molecules on undifferentiated cell growth and tumor progression. Here we demonstrate that cell surface expression of CEACAM1 on confluent A549 human lung adenocarcinoma cells plays a critical role in differentiated, contact-inhibited cell growth. Interestingly, CEACAM1-L, but not CEACAM1-S, negatively regulates proliferation via its ITIM domain, while in proliferating cells no CEACAM expression is detectable. Furthermore, we show for the first time that CEACAM6 acts as an inducer of cellular proliferation in A549 cells, likely by interfering with the contact-inhibiting signal triggered by CEACAM1-4L, leading to undifferentiated anchorage-independent cell growth. We also found that A549 cells expressed significant amounts of non-membrane anchored variants of CEACAM5 and CEACAM6, representing a putative source for the increased CEACAM5/6 serum levels frequently found in lung cancer patients. Taken together, our data suggest that post-confluent contact inhibition is established and maintained by CEACAM1-4L, but disturbances of CEACAM1 signalling by CEACAM1-4S and other CEACAMs lead to undifferentiated cell growth and malignant transformation.
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影响因子：
8
作者：
Duxbury, MS;Ito, H;Whang, EE
通讯作者：
Whang, EE
影响因子：
4.8
作者：
Guillot, L;Medjane, S;Si-Tahar, M
通讯作者：
Si-Tahar, M
影响因子：
--
作者：
ENGER, MD;TESMER, JG;BARHAM, SS
通讯作者：
BARHAM, SS
影响因子：
6.4
作者：
GRUNERT, F;DANIEL, S;JANTSCHEFF, P
通讯作者：
JANTSCHEFF, P
影响因子：
37.3
作者：
Gaur S;Shively JE;Yen Y;Gaur RK
通讯作者：
Gaur RK