PRC1: Linking Cytokinesis, Chromosomal Instability, and Cancer Evolution

癌变 胞质分裂 细胞周期 生物 癌症研究 癌症 基因组不稳定性 癌细胞 细胞生物学 染色体不稳定性 细胞 遗传学 细胞分裂 DNA损伤 基因 DNA 染色体
作者
Jing Li,Marlene Dallmayer,Thomas Kirchner,Julian Musa,Thomas G. P. Grünewald
出处
期刊:Trends in cancer [Elsevier BV]
卷期号:4 (1): 59-73 被引量:51
标识
DOI:10.1016/j.trecan.2017.11.002
摘要

Cytokinesis defects drive carcinogenesis by creating CIN. CIN causes genetic heterogeneity within tumors and contributes to clonal cancer evolution. PRC1, a master regulator of normal cytokinesis, is deregulated in various types of cancers and this correlates with drug resistance and worse patient outcome. PRC1 emerges as a novel drug target. Targeting PRC1 may attenuate CIN in genomically unstable cancers, or drive genetically stable cancers into apoptosis via generation of genomic chaos. Cytokinesis is the final event of the cell cycle dividing one cell into two daughter cells. The protein regulator of cytokinesis (PRC)1 is essential for cytokinesis and normal cell cleavage. Deregulation of PRC1 causes cytokinesis defects that promote chromosomal instability (CIN) and thus tumor heterogeneity and cancer evolution. Consistently, abnormal PRC1 expression correlates with poor patient outcome in various malignancies, which may be caused by PRC1-mediated CIN and aneuploidy. Here, we review the physiological functions of PRC1 in cell cycle regulation and its contribution to tumorigenesis and intratumoral heterogeneity. We discuss targeting PRC1 within the complementary approaches of either normalizing CIN in aneuploid cancers or creating chromosomal chaos in genomically stable cancers to induce apoptosis. Cytokinesis is the final event of the cell cycle dividing one cell into two daughter cells. The protein regulator of cytokinesis (PRC)1 is essential for cytokinesis and normal cell cleavage. Deregulation of PRC1 causes cytokinesis defects that promote chromosomal instability (CIN) and thus tumor heterogeneity and cancer evolution. Consistently, abnormal PRC1 expression correlates with poor patient outcome in various malignancies, which may be caused by PRC1-mediated CIN and aneuploidy. Here, we review the physiological functions of PRC1 in cell cycle regulation and its contribution to tumorigenesis and intratumoral heterogeneity. We discuss targeting PRC1 within the complementary approaches of either normalizing CIN in aneuploid cancers or creating chromosomal chaos in genomically stable cancers to induce apoptosis. describes the presence of an abnormal number of chromosomes in a cell resulting in anisokaryosis (unequal shapes of the cell nuclei), which is frequently observed in cancer cells. originate from the centrosome and do not have a connection to a kinetochore, but anchor the spindle poles to the plasma membrane. is a genomic state in which chromosomes are unstable, meaning that parts of the chromosomes or even the whole chromosomes are duplicated (gain) or deleted (loss). Upon mitosis, unequal distribution of genetic information to daughter cells can result in in aneuploidy. The majority of human solid cancers is characterized by CIN. interdigitate at the spindle midzone and push the spindle poles apart via motor proteins. protein complexes assembled on both sides the centromeric region of a chromosome. Kinetochores are required for the interaction of spindle microtubules with chromosomes and proper chromosome segregation. bundles of microtubules that end at kinetochores. the only structure linking the two halves of the mitotic spindle. The midzone is initially formed between separating chromosomes by bundling of interpolar microtubules, and then compacted into an electron-dense structure called the midbody. The midzone serves as a platform or ‘landing pad’ for other critical spindle midzone proteins, such as centralspindlin and chromosomal passenger proteins involved in cytokinesis.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
橙子皮发布了新的文献求助10
刚刚
1秒前
1秒前
smottom应助甜晞采纳,获得20
2秒前
ELend完成签到,获得积分10
3秒前
jhy0803发布了新的文献求助10
3秒前
MQ发布了新的文献求助10
4秒前
hh哈哈完成签到,获得积分10
5秒前
小蘑菇应助优秀沛春采纳,获得10
5秒前
勤奋静曼完成签到 ,获得积分10
5秒前
siying发布了新的文献求助10
5秒前
6秒前
依依发布了新的文献求助10
6秒前
6秒前
橘子胡完成签到,获得积分10
7秒前
j_lan完成签到,获得积分10
9秒前
9秒前
sissiarno完成签到,获得积分0
10秒前
nglmy77完成签到 ,获得积分10
13秒前
sword完成签到,获得积分10
13秒前
NexusExplorer应助含糊的画板采纳,获得10
13秒前
13秒前
舒服的白云完成签到,获得积分10
14秒前
李李李发布了新的文献求助10
14秒前
香菜完成签到,获得积分10
14秒前
拼搏的潘子完成签到,获得积分10
16秒前
碳烤小黑茶完成签到 ,获得积分10
16秒前
siying完成签到,获得积分10
17秒前
17秒前
17秒前
18秒前
18秒前
张教授完成签到 ,获得积分10
19秒前
舒服的问萍完成签到,获得积分10
19秒前
19秒前
19秒前
深情安青应助j_lan采纳,获得10
20秒前
ding应助李李李采纳,获得10
20秒前
flame发布了新的文献求助10
20秒前
20秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3969574
求助须知:如何正确求助?哪些是违规求助? 3514435
关于积分的说明 11173986
捐赠科研通 3249755
什么是DOI,文献DOI怎么找? 1794979
邀请新用户注册赠送积分活动 875537
科研通“疑难数据库(出版商)”最低求助积分说明 804844