Targeting anoikis resistance in prostate cancer metastasis.
Targeting anoikis resistance in prostate cancer metastasis.
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DOI：
10.1016/j.mam.2010.02.001
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发表时间：
2010-04
影响因子：
10.6
通讯作者：
Kyprianou, Natasha
中科院分区：
文献类型：
--
作者：
Sakamoto, Shinichi;Kyprianou, Natasha
Anoikis是细胞凋亡的一种模式，是细胞与基质相互作用不足的结果，在肿瘤血管生成和转移中起关键作用。肿瘤细胞向转移潜能发展的过程是由整合素介导的，整合素与细胞外基质（ECM）的成分结合后，重组形成粘附复合物。靶向凋亡参与者具有巨大的治疗意义，因为对细胞凋亡的抵抗不仅对标准治疗策略的治疗失败至关重要，而且在失去锚定和脱离ECM时发生的细胞凋亡在血管生成和转移中也起着重要作用。在没有与ECM粘附的情况下存活的能力，使肿瘤细胞能够从原发肿瘤部位扩散，侵入远处部位并建立转移灶。肿瘤细胞可以通过控制外源性死亡受体途径和ecm -整合素介导的细胞存活途径，从脱离诱导的细胞凋亡中逃脱。考虑到单个信号效应器的功能混杂，解剖驱动肿瘤细胞逃避疾病并开始转移扩散的分子网络机制是至关重要的。对死亡的抵抗决定了肿瘤细胞的存活，并为转移性前列腺癌的靶向治疗提供了分子基础。进一步解剖关键的anoikis信号事件将使anoikis靶向治疗优化，在前列腺癌转移开始之前损害其转移。这篇综述将讨论anoikis在肿瘤微环境中的调控的分子理解，以及一类新型抗肿瘤药物的体内药理实施，以优化基于凋亡的治疗靶向，绕过anoikis耐药，阻碍前列腺癌的进展到转移。针对肿瘤血管的潜在联合策略（通过anoikis）和损害肿瘤起始（通过“经典”细胞凋亡），通过防止转移的发生，为转移性前列腺癌提供了强大的治疗前景。
Anoikis is a mode of apoptotic cell death, consequential to insufficient cell-matrix interactions and a critical player in tumor angiogenesis and metastasis. The events involved in tumor cell progression toward metastasis potential are mediated by integrins, which upon engagement with components of the extracellular matrix (ECM), reorganize to form adhesion complexes. Targeting apoptotic players is of immense therapeutic significance since resistance to apoptosis is not only critical in conferring therapeutic failure to standard treatment strategies, but anoikis (apoptosis upon loss of anchorage and detachment from ECM also plays an important role in angiogenesis and metastasis. The ability to survive in the absence of adhesion to the ECM, enables tumor cells to disseminate from the primary tumor site, invade a distant site and establish a metastatic lesion. Tumor cells can escape from detachment-induced apoptosis by controlling anoikis pathways, including the extrinsic death receptor pathway and the ECM-integrin mediated cell survival pathway. Considering the functional promiscuity of individual signaling effectors, it is critical to dissect the molecular networks mechanistically driving tumor cells to evade anoikis and embark on a metastatic spread. Resistance to die via anoikis dictates tumor cell survival and provides a molecular basis for therapeutic targeting of metastatic prostate cancer. Further dissection of critical anoikis signaling events will enable the therapeutic optimization of anoikis targeting to impair prostate cancer metastasis prior to its initiation. This review will discuss the molecular understanding of anoikis regulation in the tumor microenvironment and the in vivo pharmacological implementation of a novel class of antitumor-drugs to optimize apoptotic-based therapeutic targeting, bypassing anoikis-resistance to impair prostate cancer progression to metastasis. Potential combination strategies targeting tumor vascularity (via anoikis) and impairing tumor initiation (via “classic” apoptosis), provide strong therapeutic promise for metastatic prostate cancer by preventing the onset of metastasis.
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影响因子：
3.9
作者：
Brodeur, GM;Nakagawara, A;Evans, AE
通讯作者：
Evans, AE
影响因子：
4.5
作者：
Boccon-Gibod, Laurent;Hammerer, Peter;Tunn, Ulf
通讯作者：
Tunn, Ulf
影响因子：
11.2
作者：
Duxbury, MS;Ito, H;Whang, EE
通讯作者：
Whang, EE
DOI：
10.1016/s0889-8588(05)70229-x
发表时间：
2001-06-01
影响因子：
2.4
作者：
DiPaola, RS;Patel, J;Rafi, MM
通讯作者：
Rafi, MM
影响因子：
15.3
作者：
Enders, A;Bouillet, P;Puthalakath, H;Xu, YK;Tarlinton, DM;Strasser, A
通讯作者：
Strasser, A