PMID- 34293937
OWN - NLM
STAT- MEDLINE
DCOM- 20211227
LR  - 20220716
IS  - 1535-3699 (Electronic)
IS  - 1535-3702 (Print)
IS  - 1535-3699 (Linking)
VI  - 246
IP  - 23
DP  - 2021 Dec
TI  - Overexpression of HOXA10 promotes the growth and metastasis of nasopharyngeal 
      carcinoma.
PG  - 2454-2462
LID - 10.1177/15353702211030854 [doi]
AB  - Deregulation of HOX transcription factor family has frequently been observed in 
      multiple human cancers; however, their role in nasopharyngeal carcinoma remains 
      largely unclear. In the present study, we found that HOX gene family is 
      consistently upregulated in nasopharyngeal carcinoma and identified HOXA10 as one 
      of the mostly upregulated HOX genes. Importantly, we show that HOXA10 
      overexpression is associated with transcriptional activation of multiple 
      oncogenes essential for nasopharyngeal carcinoma carcinogenesis, including 
      S-phase kinase-associated protein 2 (SKP2), calcium/calmodulin-dependent protein 
      kinase kinase 2 (CAMKK2), and matrix metalloproteinase 1 (MMP1). Mechanistically, 
      the overexpression of SKP2 induces the degradation of cell cycle inhibitor p27, 
      leading to rapid cell cycle progression and cell proliferation. The 
      overexpression of CAMKK2 is associated with enhanced mTOR signaling activity to 
      meet the increased demand for proteins synthesis in rapid growing nasopharyngeal 
      carcinoma cells. Moreover, MMP1 overexpression facilitates nasopharyngeal 
      carcinoma cell migration and invasion and contributes to cancer metastasis and 
      progression. We thus concluded that HOXA10 overexpression promotes the growth and 
      metastasis of nasopharyngeal carcinoma by transcriptionally activating various 
      oncogenic pathways.
FAU - Gong, Dan
AU  - Gong D
AD  - Department of Oncology, the Second Affiliated Hospital of Nanchang University, 
      Nanchang 330006, China.
AD  - Jiangxi Key Laboratory of Clinical and Translational Cancer Research, Nanchang 
      330006, China.
FAU - Zhu, Hui
AU  - Zhu H
AD  - Department of Breast Cancer Surgery, Jiangxi Provincial Cancer Hospital, Nanchang 
      330029, China.
FAU - Zeng, Lei
AU  - Zeng L
AD  - Department of Oncology, the Second Affiliated Hospital of Nanchang University, 
      Nanchang 330006, China.
AD  - Jiangxi Key Laboratory of Clinical and Translational Cancer Research, Nanchang 
      330006, China.
FAU - Hu, Ronghuan
AU  - Hu R
AD  - Department of Oncology, the Second Affiliated Hospital of Nanchang University, 
      Nanchang 330006, China.
AD  - Jiangxi Key Laboratory of Clinical and Translational Cancer Research, Nanchang 
      330006, China.
FAU - Hu, Jiali
AU  - Hu J
AD  - Department of Oncology, the Second Affiliated Hospital of Nanchang University, 
      Nanchang 330006, China.
AD  - Jiangxi Key Laboratory of Clinical and Translational Cancer Research, Nanchang 
      330006, China.
FAU - Ding, Jianwu
AU  - Ding J
AUID- ORCID: 0000-0001-7882-1309
AD  - Department of Oncology, the Second Affiliated Hospital of Nanchang University, 
      Nanchang 330006, China.
AD  - Jiangxi Key Laboratory of Clinical and Translational Cancer Research, Nanchang 
      330006, China.
LA  - eng
PT  - Journal Article
DEP - 20210722
PL  - Switzerland
TA  - Exp Biol Med (Maywood)
JT  - Experimental biology and medicine (Maywood, N.J.)
JID - 100973463
RN  - 0 (Homeobox A10 Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (S-Phase Kinase-Associated Proteins)
RN  - 0 (SKP2 protein, human)
RN  - 140441-81-2 (HOXA10 protein, human)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.17 (CAMKK2 protein, human)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Kinase)
RN  - EC 3.4.24.7 (MMP1 protein, human)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
SB  - IM
MH  - Calcium-Calmodulin-Dependent Protein Kinase Kinase/genetics/metabolism
MH  - Carcinogenesis/*genetics
MH  - Cell Line, Tumor
MH  - Cell Movement/genetics
MH  - Cell Proliferation/genetics
MH  - Cyclin-Dependent Kinase Inhibitor p27/metabolism
MH  - Homeobox A10 Proteins/genetics/*metabolism
MH  - Humans
MH  - Matrix Metalloproteinase 1/genetics/metabolism
MH  - Nasopharyngeal Carcinoma/genetics/*pathology
MH  - Nasopharyngeal Neoplasms/genetics/*pathology
MH  - RNA Interference
MH  - RNA, Small Interfering/genetics
MH  - S-Phase Kinase-Associated Proteins/genetics/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Transcriptional Activation/genetics
MH  - Up-Regulation/genetics
PMC - PMC8649939
OTO - NOTNLM
OT  - CAMKK2
OT  - HOX genes
OT  - HOXA10
OT  - MMP1
OT  - Nasopharyngeal carcinoma
OT  - SKP2
COIS- DECLARATION OF CONFLICTING INTERESTS: The author(s) declared no potential 
      conflicts of interest with respect to the research, authorship, and/or 
      publication of this article.
EDAT- 2021/07/24 06:00
MHDA- 2021/12/28 06:00
PMCR- 2022/06/01
CRDT- 2021/07/23 05:28
PHST- 2021/07/24 06:00 [pubmed]
PHST- 2021/12/28 06:00 [medline]
PHST- 2021/07/23 05:28 [entrez]
PHST- 2022/06/01 00:00 [pmc-release]
AID - 10.1177_15353702211030854 [pii]
AID - 10.1177/15353702211030854 [doi]
PST - ppublish
SO  - Exp Biol Med (Maywood). 2021 Dec;246(23):2454-2462. doi: 
      10.1177/15353702211030854. Epub 2021 Jul 22.