Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0027627 (
metastases
)
103,950
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Metastasis
is a major cause of death in patients with colorectal cancer (CRC).
Cysteine-rich protein 2
(
CSRP2
) has been recently implicated in the progression and metastasis of a variety of cancers. However, the biological functions and underlying mechanisms of
CSRP2
in the regulation of CRC progression are largely unknown.
Methods:
Immunohistochemistry, quantitative real-time polymerase chain reaction (qPCR) and Western blotting (WB) were used to detect the expression of
CSRP2
in CRC tissues and paracancerous tissues.
CSRP2
function in CRC was determined by a series of functional tests
in vivo
and
in vitro
. WB and immunofluorescence were used to determine the relation between
CSRP2
and epithelial-mesenchymal transition (EMT). Co-immunoprecipitation and scanning electron microscopy were used to study the molecular mechanism of
CSRP2
in CRC.
Results:
The
CSRP2
expression level in CRC tissues was lower than in adjacent normal tissues and indicated poor prognosis in CRC patients. Functionally,
CSRP2
could suppress the proliferation, migration, and invasion of CRC cells
in vitro
and inhibit CRC tumorigenesis and metastasis
in vivo
. Mechanistic investigations revealed a physical interaction between
CSRP2
and p130Cas.
CSRP2
could inhibit the activation of Rac1 by preventing the phosphorylation of p130Cas, thus activating the Hippo signaling pathway, and simultaneously inhibiting the ERK and PAK/LIMK/cortactin signaling pathways, thereby inhibiting the EMT and metastasis of CRC. Rescue experiments showed that blocking the p130Cas and Rac1 activation could inhibit EMT induced by
CSRP2
silencing.
Conclusion:
Our results suggest that the
CSRP2
/p130Cas/Rac1 axis can inhibit CRC aggressiveness and metastasis through the Hippo, ERK, and PAK signaling pathways. Therefore,
CSRP2
may be a potential therapeutic target for CRC.
...
PMID:CSRP2 suppresses colorectal cancer progression
via
p130Cas/Rac1 axis-meditated ERK, PAK, and HIPPO signaling pathways. 3304 70
