The doctrine of＇the golden mean＇ of the Confucian certainly applies at the molecular level to cell growth and migration. It is critically important for tissue architecture and homeostasis that cells stop prolifera- ...The doctrine of＇the golden mean＇ of the Confucian certainly applies at the molecular level to cell growth and migration. It is critically important for tissue architecture and homeostasis that cells stop prolifera- tion when reaching appropriate density and halt migration in a direction to avoid collision with others. This ＇red light＇ to hinder cell movement is essential for maintaining contact inhibition of locomotion （CIL）--a phe- nomenon that a cell ceases to continue moving in the same direction when it comes into contact with another cell. The concept of CIL emerged initially from the early work of Abercrombie and Heaysman in the 1950s.展开更多
The histone methyltransferase EZH2 has been in the limelight of the fi eld of cancer epigenetics for a decade now since it was fi rst discovered to exhibit an elevated expression in metastatic prostate cancer.It persi...The histone methyltransferase EZH2 has been in the limelight of the fi eld of cancer epigenetics for a decade now since it was fi rst discovered to exhibit an elevated expression in metastatic prostate cancer.It persists to attract much scientifi c attention due to its important role in the process of cancer development and its potential of being an effective therapeutic target.Thus here we review the dysregulation of EZH2 in prostate cancer,its function,upstream regulators,downstream effectors,and current status of EZH2-targeting approaches.This review there-fore provides a comprehensive overview of EZH2 in the context of prostate cancer.展开更多
Androgen receptor (AR), a hormonal transcription factor, plays important roles during prostate cancer progression and is a key target for therapeutic interventions. While androgen-deprivation therapies are initially s...Androgen receptor (AR), a hormonal transcription factor, plays important roles during prostate cancer progression and is a key target for therapeutic interventions. While androgen-deprivation therapies are initially successful in regressing prostate tumors, the disease ultimately comes back as castration-resistant prostate cancer (CRPC) or at the late stage as neuroendocrine prostate cancer (NEPC). CRPC remains largely dependent on hyperactive AR signaling in the milieu of low androgen, while NEPC is negative of AR expression but positive of many AR-repressed genes. Recent technological advances in genome-wide analysis of transcription factor binding sites have revealed an unprecedented set of AR target genes. In addition to its well-known function in activating gene expression, AR is increasingly known to also act as a transcriptional repressor. Here, we review the molecular mechanisms by which AR represses gene expression. We also summarize AR-repressed genes that are aberrantly upregulated in CRPC and NEPC and represent promising targets for therapeutic intervention.展开更多
FOXA1(also known as hepatocyte nuclear factor 3a,or HNF-3a)is a protein of the FKHD family transcription factors.FOXA1 has been termed as a pioneer transcription factor due to its unique ability of chromatin remodelin...FOXA1(also known as hepatocyte nuclear factor 3a,or HNF-3a)is a protein of the FKHD family transcription factors.FOXA1 has been termed as a pioneer transcription factor due to its unique ability of chromatin remodeling in which the chromatin can be decompacted to allow genomic access by nuclear hormone receptors,including androgen receptor(AR)and estrogen receptor(ER).In this review,we discuss our current understanding of FOXA1 regulation of prostatic and non-prostatic AR-chromatin targeting.We present an updated model wherein FOXA1:AR equilibrium in the nuclei defines prostatic AR binding profile,which is perturbed in prostate cancer with FOXA1 and/or AR de-regulation.Finally,we discuss recent efforts in exploring new horizons of AR-independent functions of FOXA1 in prostate cancer and interesting directions to pursue in future studies.展开更多
文摘The doctrine of＇the golden mean＇ of the Confucian certainly applies at the molecular level to cell growth and migration. It is critically important for tissue architecture and homeostasis that cells stop prolifera- tion when reaching appropriate density and halt migration in a direction to avoid collision with others. This ＇red light＇ to hinder cell movement is essential for maintaining contact inhibition of locomotion （CIL）--a phe- nomenon that a cell ceases to continue moving in the same direction when it comes into contact with another cell. The concept of CIL emerged initially from the early work of Abercrombie and Heaysman in the 1950s.
文摘The histone methyltransferase EZH2 has been in the limelight of the fi eld of cancer epigenetics for a decade now since it was fi rst discovered to exhibit an elevated expression in metastatic prostate cancer.It persists to attract much scientifi c attention due to its important role in the process of cancer development and its potential of being an effective therapeutic target.Thus here we review the dysregulation of EZH2 in prostate cancer,its function,upstream regulators,downstream effectors,and current status of EZH2-targeting approaches.This review there-fore provides a comprehensive overview of EZH2 in the context of prostate cancer.
文摘Androgen receptor (AR), a hormonal transcription factor, plays important roles during prostate cancer progression and is a key target for therapeutic interventions. While androgen-deprivation therapies are initially successful in regressing prostate tumors, the disease ultimately comes back as castration-resistant prostate cancer (CRPC) or at the late stage as neuroendocrine prostate cancer (NEPC). CRPC remains largely dependent on hyperactive AR signaling in the milieu of low androgen, while NEPC is negative of AR expression but positive of many AR-repressed genes. Recent technological advances in genome-wide analysis of transcription factor binding sites have revealed an unprecedented set of AR target genes. In addition to its well-known function in activating gene expression, AR is increasingly known to also act as a transcriptional repressor. Here, we review the molecular mechanisms by which AR represses gene expression. We also summarize AR-repressed genes that are aberrantly upregulated in CRPC and NEPC and represent promising targets for therapeutic intervention.
基金JY acknowledges funding from the NIH(R01CA172384)the U.S.Department of Defense(W81XWH-13-1-0319 and W81XWH-14-1-0023)+1 种基金the American Cancer Society(RSG-12-085-01)Y.A.Y.was supported by the NIH/NCI training grant T32 CA09560.
文摘FOXA1(also known as hepatocyte nuclear factor 3a,or HNF-3a)is a protein of the FKHD family transcription factors.FOXA1 has been termed as a pioneer transcription factor due to its unique ability of chromatin remodeling in which the chromatin can be decompacted to allow genomic access by nuclear hormone receptors,including androgen receptor(AR)and estrogen receptor(ER).In this review,we discuss our current understanding of FOXA1 regulation of prostatic and non-prostatic AR-chromatin targeting.We present an updated model wherein FOXA1:AR equilibrium in the nuclei defines prostatic AR binding profile,which is perturbed in prostate cancer with FOXA1 and/or AR de-regulation.Finally,we discuss recent efforts in exploring new horizons of AR-independent functions of FOXA1 in prostate cancer and interesting directions to pursue in future studies.
