scholarly journals Identification of TRPV4 as a novel target in invasiveness of colorectal cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Peng Zhang ◽  
Jian Xu ◽  
Hua Zhang ◽  
Xiao-Yu Liu
Keyword(s):  
Colon Cancer ◽  
Cell Migration ◽  
Critical Role ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Cancer Invasiveness ◽  
Cell Invasiveness ◽  
Novel Target ◽  
Local Metastasis

Abstract Background Emerging evidence has indicated the critical role of TRPV4 in diverse human cancers. However, the underlying molecular mechanism of TRPV4 in colon cancer invasiveness is still unknown. Methods Immunohistochemistry staining was used to analyze the expression of TRPV4 and ZEB1 in clinical tissues; Wound healing and transwell assays were applied to determine the cell invasiveness; Western blot was used to explore the relation between TRPV4 and ZEB1. Results Colon cancer cells were transfected with siRNA against TRPV4 or HC067047 (a selective TRPV4 antagonist), TRPV4 full-length plasmid or siRNA against ZEB1, or both, in order to measure cell migration and invasion. And we found that TRPV4 silencing or inhibition exhibited an inhibitory role in colon cancer cell migration and invasion, coupled with compromised EMT process, and suppressed AKT activity. TRPV4 stimulated expression of ZEB1 and consequently contributed to EMT process and invasiveness. It was also revealed that overexpression of TRPV4 and ZEB1 in clinical patients with local metastasis, and positive correlation between TRPV4 and ZEB1. Conclusions Our results uncovered the role of TRPV4 in tumor metastasis and highlighted the potential mechanism of TRPV4-ZEB1 axis in indicating EMT.

scholarly journals MicroRNA-340-5p inhibits colon cancer cell migration via targeting of RhoA

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Anwar Algaber ◽  
Amr Al-Haidari ◽  
Raed Madhi ◽  
Milladur Rahman ◽  
Ingvar Syk ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Migration ◽  
Cancer Cell ◽  
Colon Cancer Cell ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Colon Cancer Cells ◽  
Cell Migration And Invasion ◽  
Ht 29

Abstract Colon cancer is the third most common cancer and a significant cause of cancer-related deaths worldwide. Metastasis is the most insidious aspect of cancer progression. Convincing data suggest that microRNAs (miRs) play a key function in colon cancer biology. We examined the role of miR-340-5p in regulating RhoA expression as well as cell migration and invasion in colon cancer cells. Levels of miR-340-5p and RhoA mRNA varied inversely in serum-free and serum-grown HT-29 and AZ-97 colon cancer cells. It was found transfection with miR-340-5p not only decreased expression of RhoA mRNA and protein levels in HT-29 cells but also reduced colon cancer cell migration and invasion. Bioinformatics analysis predicted one putative binding sites at the 3′-UTR of RhoA mRNA. Targeting this binding site with a specific blocker reversed mimic miR-340-5p-induced inhibition of RhoA activation and colon cancer cell migration and invasion. These novel results suggest that miR-340-5p is an important regulator of colon cancer cell motility via targeting of RhoA and further experiments are warranted to evaluate the role of miR-340-5p in colon cancer metastasis.

scholarly journals Cooperation of SRPK2, Numb and p53 in the malignant biology and chemosensitivity of colorectal cancer

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Guosen Wang ◽  
Weiwei Sheng ◽  
Jingtong Tang ◽  
Xin Li ◽  
Jianping Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Chemical Agent ◽  
Cell Migration And Invasion ◽  
Agent Treatment ◽  
Hct116 Cells

Abstract Serine-arginine protein kinase 2 (SRPK2) is aberrantly expressed in human malignancies including colorectal cancer (CRC). However, little is known about the molecular mechanisms, and the role of SRPK2 in chemosensitivity remains unexplored in CRC. We recently showed that SRPK2 promotes pancreatic cancer progression by down-regulating Numb and p53. Therefore, we investigated the cooperation between SRPK2, Numb and p53 in the cell migration, invasion and chemosensitivity of CRC in vitro. Here, we showed that SRPK2 expression was higher in CRC tumors than in nontumor tissues. SRPK2 expression was positively associated with clinicopathological characteristics of CRC patients, including tumor differentiation, T stage, N stage and UICC stage. Additionally, SRPK2 had no association with mutant p53 (mtp53) in SW480 and SW620 cells, but negatively regulated Numb and wild-type p53 (wtp53) in response to 5-fluorouracil or cisplatin treatment in HCT116 cells. Moreover, SRPK2, Numb and p53 coimmunoprecipitated into a triple complex with or without the treatment of 5-fluorouracil in HCT116 cells, and p53 knockdown reversed the up-regulation of wtp53 induced by SRPK2 silencing with chemical agent treatment. Furthermore, overexpression of SRPK2 increased cell migration and invasion and decreased chemosensitivity to 5-fluorouracil or cisplatin in HCT116 cells. Conversely, SRPK2 silencing decreased cell migration and invasion and increased chemosensitivity to 5-fluorouracil or cisplatin, yet these effects could be reversed by p53 knockdown under chemical agent treatment. These results thus reveal a novel role of SRPK2-Numb-p53 signaling in the progression of CRC and demonstrate that SRPK2 is a potential therapeutic target for CRC clinical therapy.

scholarly journals Role of KCa3.1 Channels in Modulating Ca2+ Oscillations during Glioblastoma Cell Migration and Invasion

2018 ◽  
Vol 19 (10) ◽  
pp. 2970 ◽  
Author(s):  
Luigi Catacuzzeno ◽  
Fabio Franciolini
Keyword(s):  
Cell Migration ◽  
Theoretical Model ◽  
Migration And Invasion ◽  
Channel Activity ◽  
Cell Migration And Invasion ◽  
Channel Modulation ◽  
Invasion Mechanisms ◽  
Migratory Cycle ◽  
Channel Dependent

Cell migration and invasion in glioblastoma (GBM), the most lethal form of primary brain tumors, are critically dependent on Ca2+ signaling. Increases of [Ca2+]i in GBM cells often result from Ca2+ release from the endoplasmic reticulum (ER), promoted by a variety of agents present in the tumor microenvironment and able to activate the phospholipase C/inositol 1,4,5-trisphosphate PLC/IP3 pathway. The Ca2+ signaling is further strengthened by the Ca2+ influx from the extracellular space through Ca2+ release-activated Ca2+ (CRAC) currents sustained by Orai/STIM channels, meant to replenish the partially depleted ER. Notably, the elevated cytosolic [Ca2+]i activates the intermediate conductance Ca2+-activated K (KCa3.1) channels highly expressed in the plasma membrane of GBM cells, and the resulting K+ efflux hyperpolarizes the cell membrane. This translates to an enhancement of Ca2+ entry through Orai/STIM channels as a result of the increased electromotive (driving) force on Ca2+ influx, ending with the establishment of a recurrent cycle reinforcing the Ca2+ signal. Ca2+ signaling in migrating GBM cells often emerges in the form of intracellular Ca2+ oscillations, instrumental to promote key processes in the migratory cycle. This has suggested that KCa3.1 channels may promote GBM cell migration by inducing or modulating the shape of Ca2+ oscillations. In accordance, we recently built a theoretical model of Ca2+ oscillations incorporating the KCa3.1 channel-dependent dynamics of the membrane potential, and found that the KCa3.1 channel activity could significantly affect the IP3 driven Ca2+ oscillations. Here we review our new theoretical model of Ca2+ oscillations in GBM, upgraded in the light of better knowledge of the KCa3.1 channel kinetics and Ca2+ sensitivity, the dynamics of the Orai/STIM channel modulation, the migration and invasion mechanisms of GBM cells, and their regulation by Ca2+ signals.

scholarly journals Down-regulation of microRNA-34a-5p promotes trophoblast cell migration and invasion via targetting Smad4

2019 ◽  
Vol 39 (2) ◽  
Author(s):  
Fang Xue ◽  
Jing Yang ◽  
Qirong Li ◽  
Haibin Zhou
Keyword(s):  
Cell Migration ◽  
Expression Profiles ◽  
Trophoblast Cell ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Invasion And Migration ◽  
Luciferase Activity Assay ◽  
Cell Invasiveness ◽  
And Migration ◽  
Mirnas Expression

Abstract Trophoblastic dysfunction, such as insufficient migration and invasion, is well-known to be correlated with preeclampsia (PE). Recently, microRNAs (miRNAs) have been implicated in diverse biological processes and human diseases, including PE. However, the expression and functions of miRNAs in the progression of PE, especially in the regulation of trophoblast cell migration and invasion remain largely unclear. Here, we compared the miRNAs expression profiles of PE patients with healthy controls using microarray assay and chose a significant increased miRNA-miR-34a-5p for further investigation. Overexpression of miR-34a-5p dramatically reduced migration and invasion in trophoblast HTR-8/SVneo cells, whereas enhanced by its inhibitor. Luciferase activity assay showed that miR-34a-5p directly target Smad family member 4 (Smad4), which is associated with cancer cell invasiveness and metastasis. We also found that Smad4 was down-regulated in PE patients, and an inverse relationship between Smad4 and miR-34a-5p expression levels was observed in placental tissues from PE patients. Further study showed that knockdown of Smad4 effectively attenuated the promoting effects of miR-34a-5p inhibition on the migration and invasion of HTR-8/SVneo cells. Taken together, these findings suggest that inhibition of miR-34a-5p improves invasion and migration of trophoblast cells by directly targetting Smad4, which indicated the potential of miR-34a-5p as a therapeutic target against PE.

scholarly journals Verticillin A inhibits colon cancer cell migration and invasion by targeting c-Met

2020 ◽  
Vol 21 (10) ◽  
pp. 779-795
Author(s):  
Qian-qian Liu ◽  
Xue-li Zeng ◽  
Yue-lin Guan ◽  
Jing-xin Lu ◽  
Kai Tu ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Migration ◽  
Cancer Cell ◽  
Colon Cancer Cell ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Cell Migration And Invasion
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