Our data reveal a new role for PRL-3 as a key regulator of histone demethylation. JMJD1B seems to be a candidate tumour suppressor and JMJD2B seems to be a potential oncoprotein in the development and progression of CRC.
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.
Two novel chiral β‐ketoiminate‐based boron hybrid polymers, P‐1 and P‐2, are synthesized from a chiral β‐ketoiminate‐based boron hybrid complex (M‐1), with 1,4‐dioctyl‐2,5‐diethynylbenzene (M‐2) and 3,6‐diethynyl‐9‐octyl‐9H‐carbazole (M‐3), respectively, via a Pd‐catalyzed Sonogashira coupling reaction. The resulting polymers P‐1 and P‐2 show strong fluorescence emission centered at 525 nm and 534 nm with large Stokes’ shifts and high quantum yields. Most importantly, compared with the circularly polarized luminescence (CPL) dissymmetry factor (glum = +0.042) of chiral small model molecules, P‐1 and P‐2 can exhibit a large glum as high as +0.105 and +0.349 in CH2Cl2 solution, which can be attributed to the amplification effect of CPL arising from the conjugated polymer structure.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.