scholarly journals Knockdown of SPOCK1 Inhibits the Proliferation and Invasion in Colorectal Cancer Cells by Suppressing the PI3K/Akt Pathway

2016 ◽  
Vol 24 (6) ◽  
pp. 437-445 ◽  
Author(s):  
Ping Zhao ◽  
Hai-Tao Guan ◽  
Zhi-Jun Dai ◽  
Yu-Guang Ma ◽  
Xiao-Xu Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Potential Therapeutic Target ◽  
Colorectal Cancer Cells ◽  
First Time ◽  
Proliferation In Vitro ◽  
Proliferation And Invasion ◽  
Hct116 Cells

Sparc/osteonectin, cwcv, and kazal-like domains proteoglycan (testican) 1 (SPOCK1), known as testican-1, were found to be involved in the development and progression of tumors. However, in colorectal cancer (CRC), the expression pattern of SPOCK1 and its functional role remain poorly investigated. In the present study, we explored the role of SPOCK1 in CRC. Our results demonstrated that SPOCK1 is overexpressed in CRC cell lines. SPOCK1 silencing significantly inhibited the proliferation in vitro and the tumor growth in vivo. Furthermore, SPOCK1 silencing significantly attenuated the migration/invasion by reversing the EMT process in CRC cells. Finally, knockdown of SPOCK1 obviously decreased the protein expression levels of p-PI3K and p-Akt in HCT116 cells. In total, our study demonstrated for the first time that knockdown of SPOCK1 inhibits the proliferation and invasion in CRC cells, possibly through the PI3K/Akt signaling pathway. Therefore, SPOCK1 may be a potential therapeutic target for the treatment of CRC.

scholarly journals Empty Spiracles Homeobox 2 (EMX2) Inhibits the Invasion and Tumorigenesis in Colorectal Cancer Cells

2017 ◽  
Vol 25 (4) ◽  
pp. 537-544 ◽  
Author(s):  
Yan Zhang ◽  
Gang Cao ◽  
Qing-gong Yuan ◽  
Jun-hui Li ◽  
Wen-Bin Yang
Keyword(s):  
Colorectal Cancer ◽  
Transcription Factor ◽  
Essential Role ◽  
Migration And Invasion ◽  
Human Colorectal Cancer ◽  
Potential Therapeutic Target ◽  
Colorectal Cancer Cells ◽  
Proliferation In Vitro

Empty spiracles homeobox 2 (EMX2) is a homeodomain-containing transcription factor that plays an essential role in tumorigenesis. However, to the best of our knowledge, the role of EMX2 in human colorectal cancer (CRC) is still unclear. Thus, the aim of this study was to investigate the expression and role of EMX2 in CRC. Our results demonstrated that the expression of EMX2 was greatly decreased in CRC tissues and cell lines. Overexpression of EMX2 significantly inhibited the proliferation in vitro and CRC tumor growth in nude mice. In addition, EMX2 also inhibited the migration and invasion of CRC cells. Mechanically, overexpression of EMX2 downregulated the expression levels of β-catenin, cyclin D1, and c-Myc in CRC cells. Taken together, our study demonstrates that EMX2 inhibits proliferation and tumorigenesis through inactivation of the Wnt/β-catenin pathway in CRC cells. Therefore, EMX2 may be a potential therapeutic target for the treatment of CRC.

scholarly journals 4-Acetyl-antroquinonol B Suppresses SOD2-Enhanced Cancer Stem Cell-Like Phenotypes and Chemoresistance of Colorectal Cancer Cells by Inducing hsa-miR-324 Re-Expression

2018 ◽  
Author(s):  
Oluwaseun Adebayo Bamodu ◽  
Ching-Kuo Yang ◽  
David T.W. Tzeng ◽  
Kuang-Tai Kuo ◽  
Chun-Chih Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Strategy ◽  
Aberrant Expression ◽  
Colorectal Cancer Cells ◽  
Enhanced Expression ◽  
Interfering Rna ◽  
Hct116 Cells

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality in both sexes globally. This is not unconnected with the heterogeneity and plasticity of CRC stem cells (CRC-SCs) which stealthily exploit niche-related and (epi)genetic factors to facilitate metastasis, chemoresistance, tumor recurrence, and disease progression. Despite accumulating evidence of the role of dysregulated microRNAs in malignancies, the therapeutic efficacy of pharmacological-targeting of CRC-SC-associated microRNAs is relatively under-explored. Experimental approach: In this present study, we employed relatively new bioinformatics approaches, analyses of microarray data, western blot, RT-PCR, and functional assays to show that hsa-miR-324-5p expression is significantly suppressed in CRC cells, and inversely correlates with the aberrant expression of SOD2. Results: This converse hsa-miR-324-5p/SOD2 relationship is associated with enhanced oncogenicity, which is effectively inhibited by 4-AAQB as evidenced by inhibited cell viability and proliferation, as well as, attenuated migration, invasion and clonogenicity in 4-AAQB-treated DLD1 and HCT116 cells. We also showed that 4-AAQB-induced re-expression of hsa-miR-324-5p, akin to short-interfering RNA reduced SOD2 expression, correlates with the concurrent down-regulation of SOD2, N-cadherin, vimentin, c-Myc, and BcL-xL2, with concomitant up-regulation of E-cadherin and BAX2 proteins. Enhanced expression of hsa-miR-324-5p in the CRC cells suppressed their tumorigenicity in vitro and in vivo. Additionally, 4-AAQB synergistically potentiates FOLFOX anticancer effect by eliciting the re-expression of SOD2-suppressed hsa-miR-324 and inhibiting SOD2-mediated tumorigenicity. Conclusion: Our findings highlight the pre-clinical anti-CSC efficacy of 4-AAQB, with or without FOLFOX in CRC, and suggest a potential novel therapeutic strategy for CRC patients.

scholarly journals YAP inhibits autophagy and promotes progression of colorectal cancer via upregulating Bcl-2 expression

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Lan Jin ◽  
Yunhe Chen ◽  
Dan Cheng ◽  
Zhikai He ◽  
Xinyi Shi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Death ◽  
Transcriptional Coactivator ◽  
Inhibitory Protein ◽  
Potential Therapeutic Target ◽  
Related Cell ◽  
Autophagy Inhibition

AbstractColorectal cancer (CRC) is one of the most aggressive and lethal cancers. The role of autophagy in the pathobiology of CRC is intricate, with opposing functions manifested in different cellular contexts. The Yes-associated protein (YAP), a transcriptional coactivator inactivated by the Hippo tumor-suppressor pathway, functions as an oncoprotein in a variety of cancers. In this study, we found that YAP could negatively regulate autophagy in CRC cells, and consequently, promote tumor progression of CRC in vitro and in vivo. Mechanistically, YAP interacts with TEAD forming a complex to upregulate the transcription of the apoptosis-inhibitory protein Bcl-2, which may subsequently facilitate cell survival by suppressing autophagy-related cell death; silencing Bcl-2 expression could alleviate YAP-induced autophagy inhibition without affecting YAP expression. Collectively, our data provide evidence for YAP/Bcl-2 as a potential therapeutic target for drug exploration against CRC.

scholarly journals 4-Acetyl-Antroquinonol B Suppresses SOD2-Enhanced Cancer Stem Cell-Like Phenotypes and Chemoresistance of Colorectal Cancer Cells by inducing hsa-miR-324 re-Expression

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 269 ◽  
Author(s):  
Oluwaseun Adebayo Bamodu ◽  
Ching-Kuo Yang ◽  
Wei-Hong Cheng ◽  
David T.W. Tzeng ◽  
Kuang-Tai Kuo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Aberrant Expression ◽  
Colon Cells ◽  
Colorectal Cancer Cells ◽  
Enhanced Expression ◽  
Polymerase Chain ◽  
Interfering Rna

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality in both sexes globally. This is not unconnected with the heterogeneity and plasticity of CRC stem cells (CRC-SCs) which stealthily exploit the niche-related and (epi)genetic factors to facilitate metastasis, chemoresistance, tumor recurrence, and disease progression. Despite the accumulating evidence of the role of dysregulated microRNAs in malignancies, the therapeutic efficacy of pharmacological-targeting of CRC-SC-associated microRNAs is relatively under-explored. Experimental approach: In this present study, we employed relatively new bioinformatics approaches, analyses of microarray data, Western blot, real-time polymerase chain reaction (RT-PCR), and functional assays to show that hsa-miR-324-5p expression is significantly suppressed in CRC cells, and inversely correlates with the aberrant expression of SOD2. Results: This converse hsa-miR-324-5p/SOD2 relationship is associated with enhanced oncogenicity, which is effectively inhibited by 4-acetylantroquinonol B (4-AAQB), as evidenced by inhibited cell viability and proliferation, as well as attenuated migration, invasion, and clonogenicity in 4-AAQB-treated DLD1 and HCT116 cells. Interestingly, 4-AAQB did not affect the viability and proliferation of normal colon cells. We also showed that 4-AAQB-induced re-expression of hsa-miR-324-5p, akin to short-interfering RNA, reduced SOD2 expression, correlates with the concurrent down-regulation of SOD2, N-cadherin, vimentin, c-Myc, and BcL-xL2, with concomitant up-regulation of E-cadherin and BAX2 proteins. Enhanced expression of hsa-miR-324-5p in the CRC cells suppressed their tumorigenicity in vitro and in vivo. Additionally, 4-AAQB synergistically potentiates the FOLFOX (folinate (leucovorin), fluorouracil (5FU), and oxaliplatin) anticancer effect by eliciting the re-expression of SOD2-suppressed hsa-miR-324, and inhibiting SOD2-mediated tumorigenicity. Conclusion: Our findings highlight the pre-clinical anti-CSC efficacy of 4-AAQB, with or without FOLFOX in CRC, and suggest a potential novel therapeutic strategy for CRC patients.

scholarly journals Resveratrol Suppresses Cross-Talk between Colorectal Cancer Cells and Stromal Cells in Multicellular Tumor Microenvironment: A Bridge between In Vitro and In Vivo Tumor Microenvironment Study

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4292
Author(s):  
Constanze Buhrmann ◽  
Parviz Shayan ◽  
Aranka Brockmueller ◽  
Mehdi Shakibaei
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
T Lymphocytes ◽  
Cancer Cells ◽  
T Lymphocyte ◽  
Stromal Cells ◽  
Colorectal Cancer Cells ◽  
Hct116 Cells

The interaction between tumor cells and the tumor microenvironment (TME) is an important process for the development of tumor malignancy. Modulation of paracrine cross-talk could be a promising strategy for tumor control within the TME. The exact mechanisms of multi-targeted compound resveratrol are not yet fully understood. Whether resveratrol can modulate paracrine signal transduction-induced malignancy in the multicellular-TME of colorectal cancer cells (CRC) was investigated. An in vitro model with 3D-alginate HCT116 cells in multicellular-TME cultures (fibroblast cells, T-lymphocytes) was used to elucidate the role of TNF-β, Sirt1-ASO and/or resveratrol in the proliferation, invasion and cancer stem cells (CSC) of CRC cells. We found that multicellular-TME, similar to TNF-β-TME, promoted proliferation, colony formation, invasion of CRC cells and enabled activation of CSCs. However, after co-treatment with resveratrol, the malignancy of multicellular-TME reversed to HCT116. In addition, resveratrol reduced the secretion of T-lymphocyte/fibroblast (TNF-β, TGF-β3) proteins, antagonized the T-lymphocyte/fibroblast-promoting NF-κB activation, NF-κB nuclear translocation and thus the expression of NF-κB-promoting biomarkers, associated with proliferation, invasion and survival of CSCs in 3D-alginate cultures of HCT116 cells induced by TNF-β- or multicellular-TME, but not by Sirt1-ASO, indicating the central role of this enzyme in the anti-tumor function of resveratrol. Our results suggest that in vitro multicellular-TME promotes crosstalk between CRC and stromal cells to increase survival, migration of HCT116 and the resveratrol/Sirt1 axis suppresses this loop by modulating paracrine agent secretion and NF-κB signaling. Fibroblasts and T-lymphocytes are promising targets for resveratrol in the prevention of CRC metastasis.

scholarly journals Circ_0030998 promotes tumor proliferation and angiogenesis by sponging miR-567 to regulate VEGFA in colorectal cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Longyang Jin ◽  
Chao Han ◽  
Tianyu Zhai ◽  
Xiaoyu Zhang ◽  
Chun Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Inhibitory Effect ◽  
Circular Rnas ◽  
Mechanistic Studies ◽  
Potential Therapeutic Target ◽  
Underlying Mechanisms ◽  
Proliferation In Vitro

AbstractColorectal cancer (CRC) is one of the most common malignancies worldwide. Circular RNAs (circRNAs) are involved in pathological processes, especially in the development of cancers, but the roles of circRNAs in CRC are largely unknown. In this study, we investigated the role and underlying mechanisms of Circ_0030998 in CRC cell proliferation and angiogenesis. We found that Circ_0030998 was upregulated in CRC tissues and cells, and its upregulation was related to poor prognosis in CRC patients. Circ_0030998 promoted CRC cell proliferation in vitro and in vivo, and facilitated the angiogenesis of HUVECs. Mechanistic studies demonstrated that Circ_0030998 acted as a miR-567 sponge to relieve its inhibitory effect on VEGFA. Rescue assays validated that Circ_0030998 functioned in CRC cell proliferation and angiogenesis relying on VEGFA. Our findings clarified the Circ_0030998/miR-567/VEGFA regulation axis and indicated that Circ_0030998 could be a potential therapeutic target for CRC.

scholarly journals Tripartite motif containing 25 promotes proliferation and invasion of colorectal cancer cells through TGF-β signaling

2017 ◽  
Vol 37 (4) ◽  
Author(s):  
Nianfeng Sun ◽  
Yu Xue ◽  
Ting Dai ◽  
Xiding Li ◽  
Nanxiang Zheng
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Gastric Cancer Cells ◽  
Colorectal Cancer Cells ◽  
Tripartite Motif ◽  
Proliferation And Invasion

Tripartite motif containing 25 (TRIM25) is a member of TRIM proteins and functions as an E3 (ubiquitin ligase). It has been found to act as an oncogene in gastric cancer cells and is abnormally expressed in cancers in female reproductive system. Here, we investigated the function of TRIM25 in colorectal cancer. TRIM25 was found to be significantly up-regulated in colorectal cancer tissues and cancer cell lines through real-time PCR assay. Colorectal cancer cells (CRCs) overexpressing TRIM25 exhibited a two-fold higher proliferation and migration rate compared with their parental lines in vitro. Moreover, TRIM25 also promoted tumor progression in vivo. Further study indicated that TRIM25 worked through positively regulating transforming growth factor β (TGF-β) signaling pathway to regulate the proliferation and invasion of CRCs. In summary, our results indicate that TRIM25 also acts as an oncogene in colorectal cancer and it functions through TGF-β signaling pathway. Thus, TRIM25 represents potential targets for the treatment of colorectal cancer.

scholarly journals TAp63α targeting of Lgr5 mediates colorectal cancer stem cell properties and sulforaphane inhibition

Oncogenesis ◽  
2020 ◽  
Vol 9 (10) ◽  
Author(s):  
Yue Chen ◽  
Meng-huan Wang ◽  
Jian-yun Zhu ◽  
Chun-feng Xie ◽  
Xiao-ting Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cell ◽  
Cancer Progression ◽  
Inhibitory Effect ◽  
P53 Family ◽  
First Time ◽  
Established Role

Abstract Cancer stem cells (CSCs) have an established role in cancer progression and therapeutic resistance. The p63 proteins are important transcription factors which belong to the p53 family, but their function and mechanism in CSCs remain elusive. Here, we investigated the role of TAp63α in colorectal CSCs and the effects of sulforaphane on TAp63α. We found that TAp63α was upregulated in spheres with stem cell properties compared to the parental cells. Overexpression of TAp63α promoted self-renewal capacity and enhanced CSC markers expression in colorectal sphere-forming cells. Furthermore, we showed that TAp63α directly bound to the promoter region of Lgr5 to enhance its expression and activate its downstream β-catenin pathway. Functional experiments revealed that sulforaphane suppressed the stemness of colorectal CSCs both in vitro and in vivo. Upregulation of TAp63α attenuated the inhibitory effect of sulforaphane on colorectal CSCs, indicating the role of TAp63α in sulforaphane suppression of the stemness in colorectal cancer. The present study elucidated for the first time that TAp63α promoted CSCs through targeting Lgr5/β-catenin axis and participated in sulforaphane inhibition of the stem cell properties in colorectal cancer.

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