PMID- 35064934
OWN - NLM
STAT- MEDLINE
DCOM- 20220419
LR  - 20220616
IS  - 1523-4681 (Electronic)
IS  - 0884-0431 (Linking)
VI  - 37
IP  - 4
DP  - 2022 Apr
TI  - Estrogen-Responsive Gene MAST4 Regulates Myeloma Bone Disease.
PG  - 711-723
LID - 10.1002/jbmr.4507 [doi]
AB  - Our previous data showed that young female multiple myeloma (MM) patients had a 
      low frequency of osteolytic lesions. Based on this clinical observation, we found 
      that estrogen cell signaling played a regulatory role in MM bone disease (MMBD), 
      and the estrogen-responsive gene microtubule-associated serine/threonine kinase 
      family member 4 (MAST4) was a critical factor. The presence of estrogen in cell 
      cultures promoted MAST4 expression in MM cells, while knocking down estrogen 
      receptor 1 (ESR1) inhibited MAST4 expression. Chromatin immunoprecipitation assay 
      suggested a binding site of ESR1 on the MAST4 promoter. Bisphosphonates, such as 
      zoledronic acid (ZOL), which was widely used in MMBD control, could stimulate 
      MAST4 expression in MM cells by promoting ESR1 expression. MAST4 interacted with 
      phosphatase and tensin homolog (PTEN), therefore regulating the PI3K-Akt-mTOR 
      pathway and the expression of downstream cytokines, such as CCL2/3/4. MAST4 
      knockdown (MAST4-KD) or ESR1 knockdown (ESR1-KD) MM cells had repressed PTEN 
      activity, elevated PI3K-Akt-mTOR activity, and increased CCL2/3/4 expressions. 
      Coculture of MAST4-KD or ESR1-KD MM cells with pre-osteoclasts (pre-OCs) 
      stimulated OC formation in vitro, whereas neutralizing antibodies of CCL2/3/4 
      attenuated such stimulation. In mouse models, mice inoculated with MAST4-KD or 
      ESR1-KD MM cells had severer MMBD than control knockdown (CTR-KD). The 
      correlations between MAST4 and ESR1 expressions in MMBD, as well as related cell 
      signaling pathways, were confirmed in analyses using gene expression profiles 
      (GEPs) of patients' MM cells. The negative correlation of MAST4 expression and 
      occurrence of MMBD was further validated by patients' immunohistochemical tissue 
      array. Overall, our data suggested that estrogen cell signaling negatively 
      regulated MMBD through MAST4. (c) 2022 American Society for Bone and Mineral 
      Research (ASBMR).
CI  - (c) 2022 American Society for Bone and Mineral Research (ASBMR).
FAU - Cui, Yushan
AU  - Cui Y
AD  - Department of Hematology, West China Hospital/State Key Laboratory of Biotherapy 
      and Cancer Center, Sichuan University, Chengdu, China.
FAU - Wang, Fangfang
AU  - Wang F
AD  - Department of Hematology, West China Hospital/State Key Laboratory of Biotherapy 
      and Cancer Center, Sichuan University, Chengdu, China.
FAU - Zhang, Danfeng
AU  - Zhang D
AD  - Department of Hematology, West China Hospital/State Key Laboratory of Biotherapy 
      and Cancer Center, Sichuan University, Chengdu, China.
AD  - Department of Hematology, The First Affiliated Hospital, Zhengzhou University, 
      Zhengzhou, China.
FAU - Huang, Jingcao
AU  - Huang J
AD  - Department of Hematology, West China Hospital/State Key Laboratory of Biotherapy 
      and Cancer Center, Sichuan University, Chengdu, China.
FAU - Yang, Yan
AU  - Yang Y
AD  - Department of Hematology, West China Hospital/State Key Laboratory of Biotherapy 
      and Cancer Center, Sichuan University, Chengdu, China.
FAU - Xu, Juan
AU  - Xu J
AD  - Department of Hematology, West China Hospital/State Key Laboratory of Biotherapy 
      and Cancer Center, Sichuan University, Chengdu, China.
FAU - Gao, Yuhan
AU  - Gao Y
AD  - Department of Hematology, West China Hospital/State Key Laboratory of Biotherapy 
      and Cancer Center, Sichuan University, Chengdu, China.
FAU - Ding, Hong
AU  - Ding H
AD  - Department of Hematology, West China Hospital/State Key Laboratory of Biotherapy 
      and Cancer Center, Sichuan University, Chengdu, China.
FAU - Qu, Ying
AU  - Qu Y
AD  - Department of Hematology, West China Hospital/State Key Laboratory of Biotherapy 
      and Cancer Center, Sichuan University, Chengdu, China.
FAU - Zhang, Wenyan
AU  - Zhang W
AD  - Department of Pathology, West China Hospital, Sichuan University, Chengdu, China.
FAU - Liu, Weiping
AU  - Liu W
AD  - Department of Pathology, West China Hospital, Sichuan University, Chengdu, China.
FAU - Pan, Ling
AU  - Pan L
AD  - Department of Hematology, West China Hospital/State Key Laboratory of Biotherapy 
      and Cancer Center, Sichuan University, Chengdu, China.
FAU - Zhang, Li
AU  - Zhang L
AD  - Department of Hematology, West China Hospital/State Key Laboratory of Biotherapy 
      and Cancer Center, Sichuan University, Chengdu, China.
FAU - Liu, Zhigang
AU  - Liu Z
AD  - Department of Hematology, West China Hospital/State Key Laboratory of Biotherapy 
      and Cancer Center, Sichuan University, Chengdu, China.
FAU - Niu, Ting
AU  - Niu T
AD  - Department of Hematology, West China Hospital/State Key Laboratory of Biotherapy 
      and Cancer Center, Sichuan University, Chengdu, China.
FAU - Liu, Ting
AU  - Liu T
AD  - Department of Hematology, West China Hospital/State Key Laboratory of Biotherapy 
      and Cancer Center, Sichuan University, Chengdu, China.
FAU - Zheng, Yuhuan
AU  - Zheng Y
AUID- ORCID: 0000-0002-5855-4343
AD  - Department of Hematology, West China Hospital/State Key Laboratory of Biotherapy 
      and Cancer Center, Sichuan University, Chengdu, China.
LA  - eng
GR  - ZYJC21007/1.3.5 Project for Disciplines of Excellence, West China Hospital, 
      Sichuan University/
GR  - 18PJ357/Health and Family Planning Commission of Sichuan Province/
GR  - 81870157/National Natural Science Foundation of China/
GR  - 82070219/National Natural Science Foundation of China/
GR  - 81800207/National Natural Science Foundation of China/
GR  - 2021WWB03/Translational Research Grant of NCRCH/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220211
PL  - England
TA  - J Bone Miner Res
JT  - Journal of bone and mineral research : the official journal of the American 
      Society for Bone and Mineral Research
JID - 8610640
RN  - 0 (Estrogens)
RN  - 0 (Microtubule-Associated Proteins)
RN  - EC 2.7.1.37. - (MAST4 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Estrogens
MH  - Female
MH  - Humans
MH  - Mice
MH  - Microtubule-Associated Proteins/metabolism
MH  - *Multiple Myeloma/genetics
MH  - *Osteolysis
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Protein Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - TOR Serine-Threonine Kinases
OTO - NOTNLM
OT  - BONE DISEASE
OT  - ESTROGEN
OT  - MAST4
OT  - MULTIPLE MYELOMA
OT  - ZOLEDRONIC ACID
EDAT- 2022/01/23 06:00
MHDA- 2022/04/20 06:00
CRDT- 2022/01/22 12:06
PHST- 2022/01/04 00:00 [revised]
PHST- 2021/03/23 00:00 [received]
PHST- 2022/01/12 00:00 [accepted]
PHST- 2022/01/23 06:00 [pubmed]
PHST- 2022/04/20 06:00 [medline]
PHST- 2022/01/22 12:06 [entrez]
AID - 10.1002/jbmr.4507 [doi]
PST - ppublish
SO  - J Bone Miner Res. 2022 Apr;37(4):711-723. doi: 10.1002/jbmr.4507. Epub 2022 Feb 
      11.