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IQ-domain GTPase-activating protein 1 promotes the malignant phenotype of invasive ductal breast carcinoma via canonical Wnt pathway.

Abstract IQ-domain GTPase-activating protein 1 is a scaffolding protein with multidomain which plays a role in modulating dishevelled (Dvl) nuclear translocation in canonical Wnt pathway. However, the biological function and mechanism of IQ-domain GTPase-activating protein 1 in invasive ductal carcinoma (IDC) remain unknown. In this study, we found that IQ-domain GTPase-activating protein 1 expression was elevated in invasive ductal carcinoma, which was positively correlated with tumor grade, lymphatic metastasis, and poor prognosis. Coexpression of IQ-domain GTPase-activating protein 1 and Dvl in the nucleus and cytoplasm of invasive ductal carcinoma was significantly correlated but not in the membrane. Postoperative survival in the patients with their coexpression in the nucleus and cytoplasm was obviously lower than that without coexpression. The positive expression rates of c-myc and cyclin D1 were significantly higher in the patients with nuclear coexpression of Dvl and IQ-domain GTPase-activating protein 1 than that with cytoplasmic coexpression, correlating with poor prognosis. IQ-domain GTPase-activating protein 1 significantly enhanced cell proliferation and invasion in invasive ductal carcinoma cell lines by interacting with Dvl in cytoplasm to promote Dvl nuclear translocation so as to upregulate the expression of c-myc and cyclin D1. Collectively, our data suggest that IQ-domain GTPase-activating protein 1 may promote the malignant phenotype of invasive ductal carcinoma via canonical Wnt signaling, and it could be used as a potential prognostic biomarker for breast cancer patients.
PMID
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Authors

Mayor MeshTerms
Keywords

Dvl

IQ-domain GTPase-activating protein 1

c-myc

cyclin D1

invasive ductal breast carcinoma

Journal Title tumour biology : the journal of the international society for oncodevelopmental biology and medicine
Publication Year Start




PMID- 28618949
OWN - NLM
STAT- MEDLINE
DA  - 20170616
DCOM- 20170622
LR  - 20170622
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
VI  - 39
IP  - 6
DP  - 2017 Jun
TI  - IQ-domain GTPase-activating protein 1 promotes the malignant phenotype of
      invasive ductal breast carcinoma via canonical Wnt pathway.
PG  - 1010428317705769
LID - 10.1177/1010428317705769 [doi]
AB  - IQ-domain GTPase-activating protein 1 is a scaffolding protein with multidomain
      which plays a role in modulating dishevelled (Dvl) nuclear translocation in
      canonical Wnt pathway. However, the biological function and mechanism of
      IQ-domain GTPase-activating protein 1 in invasive ductal carcinoma (IDC) remain
      unknown. In this study, we found that IQ-domain GTPase-activating protein 1
      expression was elevated in invasive ductal carcinoma, which was positively
      correlated with tumor grade, lymphatic metastasis, and poor prognosis.
      Coexpression of IQ-domain GTPase-activating protein 1 and Dvl in the nucleus and 
      cytoplasm of invasive ductal carcinoma was significantly correlated but not in
      the membrane. Postoperative survival in the patients with their coexpression in
      the nucleus and cytoplasm was obviously lower than that without coexpression. The
      positive expression rates of c-myc and cyclin D1 were significantly higher in the
      patients with nuclear coexpression of Dvl and IQ-domain GTPase-activating protein
      1 than that with cytoplasmic coexpression, correlating with poor prognosis.
      IQ-domain GTPase-activating protein 1 significantly enhanced cell proliferation
      and invasion in invasive ductal carcinoma cell lines by interacting with Dvl in
      cytoplasm to promote Dvl nuclear translocation so as to upregulate the expression
      of c-myc and cyclin D1. Collectively, our data suggest that IQ-domain
      GTPase-activating protein 1 may promote the malignant phenotype of invasive
      ductal carcinoma via canonical Wnt signaling, and it could be used as a potential
      prognostic biomarker for breast cancer patients.
FAU - Zhao, Huan-Yu
AU  - Zhao HY
AD  - Department of Pathology, First Affiliated Hospital and College of Basic Medical
      Sciences, China Medical University, Shenyang, China.
FAU - Han, Yang
AU  - Han Y
AD  - Department of Pathology, First Affiliated Hospital and College of Basic Medical
      Sciences, China Medical University, Shenyang, China.
FAU - Wang, Jian
AU  - Wang J
AD  - Department of Pathology, First Affiliated Hospital and College of Basic Medical
      Sciences, China Medical University, Shenyang, China.
FAU - Yang, Lian-He
AU  - Yang LH
AD  - Department of Pathology, First Affiliated Hospital and College of Basic Medical
      Sciences, China Medical University, Shenyang, China.
FAU - Zheng, Xiao-Ying
AU  - Zheng XY
AD  - Department of Pathology, First Affiliated Hospital and College of Basic Medical
      Sciences, China Medical University, Shenyang, China.
FAU - Du, Jiang
AU  - Du J
AD  - Department of Pathology, First Affiliated Hospital and College of Basic Medical
      Sciences, China Medical University, Shenyang, China.
FAU - Wu, Guang-Ping
AU  - Wu GP
AD  - Department of Pathology, First Affiliated Hospital and College of Basic Medical
      Sciences, China Medical University, Shenyang, China.
FAU - Wang, En-Hua
AU  - Wang EH
AD  - Department of Pathology, First Affiliated Hospital and College of Basic Medical
      Sciences, China Medical University, Shenyang, China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Tumour Biol
JT  - Tumour biology : the journal of the International Society for Oncodevelopmental
      Biology and Medicine
JID - 8409922
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CCND1 protein, human)
RN  - 0 (IQ motif containing GTPase activating protein 1)
RN  - 0 (MYC protein, human)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (beta Catenin)
RN  - 0 (ras GTPase-Activating Proteins)
RN  - 136601-57-5 (Cyclin D1)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Biomarkers, Tumor/*genetics
MH  - Breast Neoplasms/*genetics/pathology/surgery
MH  - Carcinoma, Ductal/*genetics/pathology/surgery
MH  - Cyclin D1/genetics
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Lymphatic Metastasis
MH  - Middle Aged
MH  - Neoplasm Invasiveness/genetics
MH  - Prognosis
MH  - Proto-Oncogene Proteins c-myc/genetics
MH  - Survival Analysis
MH  - Wnt Signaling Pathway/genetics
MH  - beta Catenin/genetics
MH  - ras GTPase-Activating Proteins/*genetics
OTO - NOTNLM
OT  - Dvl
OT  - IQ-domain GTPase-activating protein 1
OT  - c-myc
OT  - cyclin D1
OT  - invasive ductal breast carcinoma
EDAT- 2017/06/18 06:00
MHDA- 2017/06/24 06:00
CRDT- 2017/06/17 06:00
AID - 10.1177/1010428317705769 [doi]
PST - ppublish
SO  - Tumour Biol. 2017 Jun;39(6):1010428317705769. doi: 10.1177/1010428317705769.