Abstract 1138: Aberrant expression of Plastin3 (PLS3) induces liver metastasis via enhancing the epithelial-mesenchymal transition and stemness in colorectal cancer (CRC)

2014 ◽  
Author(s):  
Masami Ueda ◽  
Keishi Sugimachi ◽  
Junji Kurashige ◽  
Shotarou Sakimura ◽  
Hidenari Hirata ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Aberrant Expression ◽  
Mesenchymal Transition

scholarly journals LncRNA SNHG16 Facilitates Liver Metastases of Colorectal Cancer by Modulating Circulating Tumor Cells (CTCs) Epithelial-Mesenchymal Transition (EMT) via a Positive Feedback Loop with YAP1/TEAD1 Complex

2020 ◽  
Author(s):  
Zhenxian Xiang ◽  
Guoquan Huang ◽  
Haitao Wu ◽  
Qiuming He ◽  
Chaogang Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Distant Metastasis ◽  
Feedback Loop ◽  
Epithelial Mesenchymal Transition ◽  
Positive Feedback Loop ◽  
Mesenchymal Transition

Abstract Background: Circulating tumor cells are important precursor of colorectal cancer metastasis, which attributes to the main cause of cancer-related death. The ability to adopt epithelial-mesenchymal transition (EMT) process facilitates CTCs generation, thereby overcoming metastatic bottlenecks and realizing distant metastasis. However, the potential molecular mechanism of CRC EMT remains largely unknown.Methods: RT-qPCR, immunohistochemical staining, and western blot were used to detect the expression of mRNA and protein in CRC. Loss- and gain-of-function approaches were performed to investigate the effect of SNHG16 on CRC cell phenotypes. Function assays, including wounding healing, transwell assay, and clone formation were used to assess the effect of SNHG16 on tumor biological behavior. Then, RNA immunoprecipitation, Chromatin Immunoprecipitation, Co-Immunoprecipitation, GST-pull down, biotin-labeled miR-195-5p pull down, and dual-luciferase assay were performed to uncover the underlying mechanism for molecular interaction. Finally, CRC nude mice xenograft model experiment was performed to evaluate the influence of SNHG16 on tumor progression in vivo Results: Compared with normal tissue and cell line, SNHG16 was significantly upregulated in CRC. Clinical investigation revealed that SNHG16 high expression was correlated with advanced TNM stage, distant metastasis, and poor prognosis of cancer patients. According to Loss- and gain-of-function experiment, SNHG16 could promote CRC proliferation, migration, invasion, EMT, mesenchymal-type CTCs (MCTCs) generation, and liver metastasis through YAP1 in vitro and in vivo. Mechanistic research indicates that, SNHG16 could act as miRNA sponge to sequester miR-195-5p on Ago2, thereby protecting YAP1 from repression and facilitating CRC liver metastasis and tumor progression. Moreover, YAP1 could combine with TEA Domain Transcription Factor 1 (TEAD1) to form a YAP1/TEAD1 complex, which could in turn bind to the promoter of SNHG16 and regulate its transcription. In addition, both of YAP1 and TEAD1 are indispensable during this process. Finally, we demonstrated that YAP1 significantly promoted the tumor progression, and SNHG16 could rescue the effect of YAP1 on tumor progressionConclusion: Herein, we clarified a hitherto unexplored positive feedback loop between SNHG16 and YAP1/TEAD1. These findings provided new sights in CRC liver metastasis, and it may act as a potential candidate in the treatment of CRC.

scholarly journals Colorectal Cancer, Liver Metastases and Biotherapies

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 894
Author(s):  
Daniel-Clement Osei-Bordom ◽  
Kamarajah Sivesh ◽  
Christou Niki
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Causes Of Death ◽  
Epithelial Mesenchymal Transition ◽  
Targeted Therapeutics ◽  
Review Of The Literature ◽  
Colorectal Cancer Liver Metastases ◽  
Mesenchymal Transition ◽  
Clinical Conditions

(1) Background: colorectal cancer (CRC) is one of the deadliest causes of death by cancer worldwide. Its first main metastatic diffusion spreads to the liver. Different mechanisms such as the epithelial–mesenchymal transition and angiogenesis are the characteristics of this invasion. At this stage, different options are possible and still in debate, especially regarding the use of targeted therapeutics and biotherapies. (2) Methods: A review of the literature has been done focusing on the clinical management of liver metastasis of colorectal cancer and the contribution of biotherapies in this field. (3) Results: In a clinical setting, surgeons and oncologists consider liver metastasis in CRC into two groups to launch adapted therapeutics: resectable and non-resectable. Around these two entities, the combination of targeted therapies and biotherapies are of high interest and are currently tested to know in which molecular and clinical conditions they have to be applied to impact positively both on survival and quality of life of patients.

scholarly journals SIRT1 promotes EMT, migration and invasion by regulating mTORC1/4E-BP1 in colorectal cancer

2020 ◽  
Author(s):  
Peifeng Liu ◽  
Xiaojing Chen ◽  
Shaolan Qin ◽  
Yan Zhou ◽  
Bo Yu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Tumors ◽  
Tumor Resection ◽  
Underlying Mechanism ◽  
Migration And Invasion ◽  
Mtor Inhibition ◽  
Primary Tumors ◽  
Mesenchymal Transition

Abstract Background Metastasis, rather than primary tumors, was accounted for the most cases of cancer death in colorectal cancer(CRC). The understanding of the underlying mechanism associated with tumor metastasis would improve the patient’s miserable fate. SIRT1 has been identified to play a role in tumorigenesis and progression of malignant tumors, especially in keeping the characteristics of cancer stem cells(CSCs) in CRC. This study was conducted to investigate the role of SIRT1 in the regulation of metastasis and the underlying mechanism in colorectal cancer. Methods We detected the expression of SIRT1 in 42 metastatic CRC patients. The relationship between SIRT1 and time to metastasis was also analyzed. Then the SIRT1 activity was regulated to investigate the liver metastasis in BALB/c mice. SIRT1 was knocked down to evaluate the effect on migration and invasion. Besides, exogenetic SIRT1 to assess the motile ability by wound healing assay and transwell assay. We then further explored the underlying mechanism. Results SIRT1 was overexpressed in 67% CRC metastatic patients and associated with reduced time to metastasis. High SIRT1 activity by resveratrol was companied with more liver metastasis in vivo. SIRT1 deficiency increased E-cadherin, while reduced Vimentin and Snail, attenuated migration and invasion significantly in CT26 and SW620 cells. Meanwhile, the exogenetic SIRT1 induced epithelial–mesenchymal transition (EMT) and elevated the migratory ability in SW480 cells. Further studies demonstrated that mTORC1 related genes were elevated while 4E-BP1 decayed by SIRT1 overexpression. The promotion of metastasis induced by SIRT1 overexpression could be abolished by mTOR inhibition, while the stemness of cells was not changed. Conclusions Collectively, our findings illustrated that SIRT1 was a functional regulator in the promotion of metastasis in CRC via mTORC1-4E-BP1 axis. SIRT1 was a potential independent prognostic factor of CRC metastatic patients after tumor resection, which provided a promising treatment target in CRC.

scholarly journals MEF2A transcriptionally upregulates the expression of ZEB2 and CTNNB1 in colorectal cancer to promote tumor progression

Oncogene ◽  
2021 ◽  
Author(s):  
Qing Xiao ◽  
Yaqi Gan ◽  
Yimin Li ◽  
Lili Fan ◽  
Jiaqi Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Formation ◽  
High Morbidity ◽  
Aberrant Expression ◽  
Mesenchymal Transition ◽  
Proliferation And Metastasis ◽  
Simultaneous Activation ◽  
Tumor Growth And Metastasis ◽  
Enhancer Factor

AbstractColorectal cancer (CRC) is one of the leading cancers worldwide, accounting for high morbidity and mortality. The mechanisms governing tumor growth and metastasis in CRC require detailed investigation. The results of the present study indicated that the transcription factor (TF) myocyte enhancer factor 2A (MEF2A) plays a dual role in promoting proliferation and metastasis of CRC by inducing the epithelial-mesenchymal transition (EMT) and activation of WNT/β-catenin signaling. Aberrant expression of MEF2A in CRC clinical specimens was significantly associated with poor prognosis and metastasis. Functionally, MEF2A directly binds to the promoter region to initiate the transcription of ZEB2 and CTNNB1. Simultaneous activation of the expression of EMT-related TFs and Wnt/β-catenin signaling by MEF2A overexpression induced the EMT and increased the frequency of tumor formation and metastasis. The present study identified a new critical oncogene involved in the growth and metastasis of CRC, providing a potential novel therapeutic target for CRC intervention.

scholarly journals Epithelial-Mesenchymal Transition and MicroRNAs in Colorectal Cancer Chemoresistance to FOLFOX

Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 75
Author(s):  
Paula I. Escalante ◽  
Luis A. Quiñones ◽  
Héctor R. Contreras
Keyword(s):  
Colorectal Cancer ◽  
Tumor Cells ◽  
Methylenetetrahydrofolate Reductase ◽  
Epithelial Mesenchymal Transition ◽  
Late Onset ◽  
Dihydropyrimidine Dehydrogenase ◽  
Acquired Resistance ◽  
Potential Effect ◽  
Mesenchymal Transition ◽  
Folfox Chemotherapy

The FOLFOX scheme, based on the association of 5-fluorouracil and oxaliplatin, is the most frequently indicated chemotherapy scheme for patients diagnosed with metastatic colorectal cancer. Nevertheless, development of chemoresistance is one of the major challenges associated with this disease. It has been reported that epithelial-mesenchymal transition (EMT) is implicated in microRNA-driven modulation of tumor cells response to 5-fluorouracil and oxaliplatin. Moreover, from pharmacogenomic research, it is known that overexpression of genes encoding dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), methylenetetrahydrofolate reductase (MTHFR), the DNA repair enzymes ERCC1, ERCC2, and XRCC1, and the phase 2 enzyme GSTP1 impair the response to FOLFOX. It has been observed that EMT is associated with overexpression of DPYD, TYMS, ERCC1, and GSTP1. In this review, we investigated the role of miRNAs as EMT promotors in tumor cells, and its potential effect on the upregulation of DPYD, TYMS, MTHFR, ERCC1, ERCC2, XRCC1, and GSTP1 expression, which would lead to resistance of CRC tumor cells to 5-fluorouracil and oxaliplatin. This constitutes a potential mechanism of epigenetic regulation involved in late-onset of acquired resistance in mCRC patients under FOLFOX chemotherapy. Expression of these biomarker microRNAs could serve as tools for personalized medicine, and as potential therapeutic targets in the future.

B7-H4 induces epithelial–mesenchymal transition and promotes colorectal cancer stemness

2021 ◽  
pp. 153323
Author(s):  
Ying Feng ◽  
Zhaoting Yang ◽  
Chengye Zhang ◽  
Nan Che ◽  
Xingzhe Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Stemness ◽  
Mesenchymal Transition

scholarly journals The microRNA-210-Stathmin1 Axis Decreases Cell Stiffness to Facilitate the Invasiveness of Colorectal Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1833
Author(s):  
Tsai-Tsen Liao ◽  
Wei-Chung Cheng ◽  
Chih-Yung Yang ◽  
Yin-Quan Chen ◽  
Shu-Han Su ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Motility ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Cell Stiffness ◽  
Mesenchymal Transition ◽  
Cytoskeletal Dynamics ◽  
Colorectal Cancer Stem Cells

Cell migration is critical for regional dissemination and distal metastasis of cancer cells, which remain the major causes of poor prognosis and death in patients with colorectal cancer (CRC). Although cytoskeletal dynamics and cellular deformability contribute to the migration of cancer cells and metastasis, the mechanisms governing the migratory ability of cancer stem cells (CSCs), a nongenetic source of tumor heterogeneity, are unclear. Here, we expanded colorectal CSCs (CRCSCs) as colonospheres and showed that CRCSCs exhibited higher cell motility in transwell migration assays and 3D invasion assays and greater deformability in particle tracking microrheology than did their parental CRC cells. Mechanistically, in CRCSCs, microRNA-210-3p (miR-210) targeted stathmin1 (STMN1), which is known for inducing microtubule destabilization, to decrease cell elasticity in order to facilitate cell motility without affecting the epithelial–mesenchymal transition (EMT) status. Clinically, the miR-210-STMN1 axis was activated in CRC patients with liver metastasis and correlated with a worse clinical outcome. This study elucidates a miRNA-oriented mechanism regulating the deformability of CRCSCs beyond the EMT process.

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