Down-regulation of DAB2IP promotes colorectal cancer invasion and metastasis by translocating hnRNPK into nucleus to enhance the transcription of MMP2.
DOC-2/DAB2 interacting protein (DAB2IP) is a RasGAP protein that shows a suppressive effect on cancer progression. Our previous study showed the involvement of transcription regulation of DAB2IP in metastasis of colorectal cancer (CRC). However, the molecular mechanisms of DAB2IP in regulating the progression of CRC need to be further explored. Here, we identified heterogeneous nuclear ribonucleoprotein K (hnRNPK) and matrix metalloproteinase 2 (MMP2) as vital downstream targets of DAB2IP in CRC cells by two-dimensional fluorescence difference gel electrophoresis and cDNA microassay, respectively. Mechanistically, down-regulation of DAB2IP increased the level of hnRNPK through MAPK/ERK signaling pathway. Subsequently, translocation of hnRNPK into nucleus enhanced the transcription activity of MMP2, and therefore promoted invasion and metastasis of CRC. Down-regulation of DAB2IP correlated negatively with hnRNPK and MMP2 expressions in CRC tissues. In conclusion, our study elucidates a novel mechanism of the DAB2IP/hnRNPK/MMP2 axis in the regulation of CRC invasion and metastasis, which may be a potential therapeutic target.
Department of Pathology, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong Province, People's Republic of China.
X H
XH
Zhu
Department of Pathology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China.
J M
JM
Wang
Department of Pathology, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong Province, People's Republic of China.
S S
SS
Yang
Department of Pathology, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong Province, People's Republic of China.
F F
FF
Wang
Department of Pathology, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong Province, People's Republic of China.
J L
JL
Hu
Department of Pathology, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong Province, People's Republic of China.
S N
SN
Xin
Department of Pathology, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong Province, People's Republic of China.
H
H
Men
Department of Pathology, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong Province, People's Republic of China.
G F
GF
Lu
Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.
X L
XL
Lan
Department of Pathology, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong Province, People's Republic of China.
D
D
Zhang
Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.
X Y
XY
Wang
Department of Pathology, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong Province, People's Republic of China.
W T
WT
Liao
Department of Pathology, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong Province, People's Republic of China.
Y Q
YQ
Ding
Department of Pathology, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong Province, People's Republic of China.
L
0000-0002-6586-8519
L
Liang
D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000235:genetics*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009362:Neoplasm Metastasis; D015398:Signal Transduction; D014158:Transcription, Genetic; D020703:ras GTPase-Activating Proteins / Q000235:genetics*
D014408:Biomarkers, Tumor; C462952:DAB2IP protein, human; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D020703:ras GTPase-Activating Proteins; C072074:HNRNPK protein, human; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
DAB2IP; MMP2; colorectal cancer; hnRNPK; metastasis