The transcription factor HOXB13 plays crucial roles in cancer development.HOXB13 is abnormally expressed in most cancers,which makes it a valuable therapeutic target for cancer therapy.The level of HOXB13 differs sign...The transcription factor HOXB13 plays crucial roles in cancer development.HOXB13 is abnormally expressed in most cancers,which makes it a valuable therapeutic target for cancer therapy.The level of HOXB13 differs significantly between healthy and cancer tissues,which indicates that the level of HOXB13 is closely related to carcinogenesis.The regulatory network mediated by HOXB13 in cancer proliferation,metastasis,and invasion has been systematically investigated.Moreover,HOXB13 variants play distinct roles in different cancers and populations.By understanding the molecular mechanisms and mutation features of HOXB13,we provide a comprehensive overview of carcinogenesis networks dependent on HOXB13.Finally,we discuss advancements in anticancer therapy targeting HOXB13 and the roles of HOXB13 in drug resistance to molecular-targeted therapies,which serves as a foundation for developing HOXB13-targeted drugs for clinical diagnosis and cancer therapies.展开更多
The recent and exciting discovery of germline HOXB13 mutations in familial prostate cancer has brought HOX signaling to the forefront of prostate cancer research.An enhanced understanding of HOX signaling,and the co-f...The recent and exciting discovery of germline HOXB13 mutations in familial prostate cancer has brought HOX signaling to the forefront of prostate cancer research.An enhanced understanding of HOX signaling,and the co-factors regulating HOX protein specificity and transcriptional regulation,has the high potential to elucidate novel approaches to prevent,diagnose,stage,and treat prostate cancer.Toward our understanding of HOX biology in prostate development and prostate cancer,basic research in developmental model systems as well as other tumor sites provides a mechanistic framework to inform future studies in prostate biology.Here we describe our current understanding of HOX signaling in genitourinary development and cancer,current clinical data of HOXB13 mutations in multiple cancers including prostate cancer,and the role of HOX protein co-factors in development and cancer.These data highlight numerous gaps in our understanding of HOX function in the prostate,and present numerous potentially impactful mechanistic and clinical opportunities for future investigation.展开更多
SNP mutations in the HOXB13 gene associated with prostate cancer were determined in Moroccans prostate cancer patients (PCa). All PCa SNP mutations were new and belong to the SNP point-mutations located on the stop co...SNP mutations in the HOXB13 gene associated with prostate cancer were determined in Moroccans prostate cancer patients (PCa). All PCa SNP mutations were new and belong to the SNP point-mutations located on the stop codon of HOXB13 exon 1 and 2 located in chromosome 17. The five mutations and their frequencies were as follows: rs1197613952 (12%), rs1597934612 (4%), rs1597933874 (4%), rs1597933837 (4%) and rs867793282 (4%). The European HOXB13-G84E (rs138213197) PCa mutation was not detected among Moroccan patients. The Y-chromosome genealogical haplotypes of the Western European (R1b1b2-M2G9) and the Eastern European (R191a-M-17) were not observed in Moroccans PCa patients. The patients have their own haplotypes E1b1 and J with a frequency of 55 and 35%, respectively. The results of the SNP mutations in the HOXB13, the absence of the HOXB13-G84E of the European in the Moroccans PCa patients, the absence of the European-lineage haplogroups (R1a1a-M17 and R1b1b2-M269) and the presence of E1b1b and J in Moroccans PCa patients would clearly indicate the absence of gene flow from European to Moroccans gene pool.展开更多
基金supported by the Top Young and Middle-aged Medical Talent of Chongqing,Top Young and Middle-aged Medical Studio of Chongqing,Chongqing Science and Health Joint fund for Top Young and Middle-aged Talent(No.2023GDRc007)the Key Project for Clinical Innovation of Army Medical University(No.CX2019LC107)the Second Affiliated Hospital of Army Military Medical University Discipline Talent Construction Special Project(No.2023XKRC007).
文摘The transcription factor HOXB13 plays crucial roles in cancer development.HOXB13 is abnormally expressed in most cancers,which makes it a valuable therapeutic target for cancer therapy.The level of HOXB13 differs significantly between healthy and cancer tissues,which indicates that the level of HOXB13 is closely related to carcinogenesis.The regulatory network mediated by HOXB13 in cancer proliferation,metastasis,and invasion has been systematically investigated.Moreover,HOXB13 variants play distinct roles in different cancers and populations.By understanding the molecular mechanisms and mutation features of HOXB13,we provide a comprehensive overview of carcinogenesis networks dependent on HOXB13.Finally,we discuss advancements in anticancer therapy targeting HOXB13 and the roles of HOXB13 in drug resistance to molecular-targeted therapies,which serves as a foundation for developing HOXB13-targeted drugs for clinical diagnosis and cancer therapies.
基金DOD PCRP PC130587(Vander Griend)NWU/UC/NSUHS Prostate SPORE(P50 CA180995)the University of Chicago Comprehensive Cancer Center(UCCCC)+2 种基金especially the Cancer Center Support Grant(P30CA014599)H.Brechka and C.Van Opstall were supported by the Cancer Biology Training Grant(T32 CA009594)R.Bhanvadia is supported by a University of Chicago Pritzker School of Medicine Fellowship.
文摘The recent and exciting discovery of germline HOXB13 mutations in familial prostate cancer has brought HOX signaling to the forefront of prostate cancer research.An enhanced understanding of HOX signaling,and the co-factors regulating HOX protein specificity and transcriptional regulation,has the high potential to elucidate novel approaches to prevent,diagnose,stage,and treat prostate cancer.Toward our understanding of HOX biology in prostate development and prostate cancer,basic research in developmental model systems as well as other tumor sites provides a mechanistic framework to inform future studies in prostate biology.Here we describe our current understanding of HOX signaling in genitourinary development and cancer,current clinical data of HOXB13 mutations in multiple cancers including prostate cancer,and the role of HOX protein co-factors in development and cancer.These data highlight numerous gaps in our understanding of HOX function in the prostate,and present numerous potentially impactful mechanistic and clinical opportunities for future investigation.
文摘SNP mutations in the HOXB13 gene associated with prostate cancer were determined in Moroccans prostate cancer patients (PCa). All PCa SNP mutations were new and belong to the SNP point-mutations located on the stop codon of HOXB13 exon 1 and 2 located in chromosome 17. The five mutations and their frequencies were as follows: rs1197613952 (12%), rs1597934612 (4%), rs1597933874 (4%), rs1597933837 (4%) and rs867793282 (4%). The European HOXB13-G84E (rs138213197) PCa mutation was not detected among Moroccan patients. The Y-chromosome genealogical haplotypes of the Western European (R1b1b2-M2G9) and the Eastern European (R191a-M-17) were not observed in Moroccans PCa patients. The patients have their own haplotypes E1b1 and J with a frequency of 55 and 35%, respectively. The results of the SNP mutations in the HOXB13, the absence of the HOXB13-G84E of the European in the Moroccans PCa patients, the absence of the European-lineage haplogroups (R1a1a-M17 and R1b1b2-M269) and the presence of E1b1b and J in Moroccans PCa patients would clearly indicate the absence of gene flow from European to Moroccans gene pool.
