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2017 ; 15
(1
): 21
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LASP2 suppresses colorectal cancer progression through JNK/p38 MAPK pathway
meditated epithelial-mesenchymal transition
#MMPMID28606091
Wang B
; Zhang L
; Zhao L
; Zhou R
; Ding Y
; Li G
; Zhao L
Cell Commun Signal
2017[Jun]; 15
(1
): 21
PMID28606091
show ga
BACKGROUND: LASP2 (LIM and SH3 Protein 2) is a small focal adhesion protein
belongs to nebulin protein family. As the newest member of nebulette family, the
function of LASP2 remains to be identified. METHODS: The relationship between
LASP2 expression and clinical characteristics of CRC was analyzed in 89
paraffin-embedded archived CRC specimens by immunohistochemistry (IHC). The
effects of LASP2 on cell growth and migration were examined in vitro, using CCK-8
and transwell assays. Western blotting was performed to examine the impact of
LASP2 on the SAPK/JNK and MAPK signaling pathways. RESULTS: In the present study,
we observed a decreased LASP2 expression in clinical colorectal cancer samples
compared with paired normal tissues. A negative correlation was also found
between LASP2 and poor prognosis of CRC patients. Gain- and loss-of-function
approaches revealed that LASP2 plays inhibitory effects on the growth and
migration of human CRC cells in vitro. Western-blot results showed that LASP2
could attenuate epithelial-mesenchymal transition (EMT) to accomplish its
suppression on CRC aggression. In LASP2 knocked down CRC cells, EMT was inhibited
along with the inactivation of JNK/p38 MAPK pathway. Consistently, treatment of
JNK inhibitor (JNK inhibitor II) together with p38 inhibitor (SB203580) could
resume the process of EMT. Interestingly, we found a negative relationship
between LASP2 and LASP1 expression in both CRC cell lines and tumors tissues,
which suggests their converse function in CRC progression. CONCLUSIONS: All the
findings indicated that LASP2 may play a significant role in suppressing CRC
progression and provided a novel biomarker for CRC therapy.
|*Disease Progression
[MESH]
|*Epithelial-Mesenchymal Transition
[MESH]
|*MAP Kinase Signaling System
[MESH]
|Carrier Proteins/*metabolism
[MESH]
|Cell Line, Tumor
[MESH]
|Cell Movement
[MESH]
|Cell Proliferation
[MESH]
|Colorectal Neoplasms/*pathology
[MESH]
|Cytoskeletal Proteins/*metabolism
[MESH]
|Down-Regulation
[MESH]
|Humans
[MESH]
|JNK Mitogen-Activated Protein Kinases/*metabolism
[MESH]
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