An insight into small extracellular vesicles: Their roles in colorectal cancer progression and potential clinical applications

A high expression of the phosphoprotein osteopontin (OPN) has been associated with cancer progression in several tumor types, including breast cancer, hepatocarcinoma, ovarian cancer, and colorectal cancer (CRC). Interestingly, OPN is overexpressed in CRC and is associated with a poor prognosis linked to invasion and metastasis. Here, we review the regulation and functions of OPN with an emphasis on CRC. We examine how epigenetic and genetic regulators interact with the key signaling pathways involved in this disease. Then, we describe the role of OPN in cancer progression, including proliferation, survival, migration, invasion, and angiogenesis. Furthermore, we outline the interest of using OPN as a clinical biomarker, and discuss if and how osteopontin can be implemented as a routine assay in clinical laboratories for monitoring CRC patients. Finally, we discuss the use of OPN an attractive, but challenging, therapeutic target.

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Tumor-derived exosomes in colorectal cancer progression and their clinical applications

Oncotarget ◽

10.18632/oncotarget.20117 ◽

2017 ◽

Vol 8 (59) ◽

pp. 100781-100790 ◽

Cited By ~ 22

Author(s):

Jianbiao Zhou ◽

Xiao-Lan Li ◽

Zhi-Rong Chen ◽

Wee-Joo Chng

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

Clinical Applications ◽

Colorectal Cancer Progression

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Revealing the changes of IgG subclass‐specific N ‐glycosylation in colorectal cancer progression by high‐throughput assay

PROTEOMICS - CLINICAL APPLICATIONS ◽

10.1002/prca.202000022 ◽

2021 ◽

pp. 2000022

Author(s):

Si Liu ◽

Yuting Yu ◽

Yuanyuan Liu ◽

Jiajing Lin ◽

Yang Fu ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

High Throughput ◽

Igg Subclass ◽

Colorectal Cancer Progression ◽

High Throughput Assay

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Decreased level of miR-1301 promotes colorectal cancer progression via activation of STAT3 pathway

Biological Chemistry ◽

10.1515/hsz-2020-0301 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Fangfang Yang ◽

Hua Wang ◽

Bianbian Yan ◽

Tong Li ◽

Lulu Min ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Migration ◽

Cancer Progression ◽

Luciferase Assay ◽

Migration And Invasion ◽

Loss Of Function ◽

Aberrant Expression ◽

Cell Migration And Invasion ◽

Lovo Cells ◽

Colorectal Cancer Progression

Abstract The molecular pathogenesis of colorectal cancer (CRC) has been widely investigated in recent years. Accumulating evidence has indicated that microRNA (miRNA) dysregulation participates in the processes of driving CRC initiation and progression. Aberrant expression of miR-1301 has been found in various tumor types. However, its role in CRC remains to be elucidated. In the present study, we identified miR-1301 was enriched in normal colorectal tissues and significantly down-regulated in CRC. Decreased level of miR-1301 strongly correlated with aggressive pathological characteristics, including advanced stage and metastasis. Bioinformatics and dual luciferase assay demonstrated that STAT3 is a direct target of miR-1301. Gain and loss-of-function assays showed that miR-1301 had no effect on cell proliferation. Overexpression of miR-1301 suppressed cell migration and invasion capacity of pSTA3-positive LoVo cells, but not pSTAT3-negative SW480 cells, while inhibition of miR-1301 consistently promoted cell migration and invasion in both cell lines. Additionally, miR-1301 inhibition restored the suppressed migration and invasion of STAT3- knockdown LoVo cells. MiR-1301 functioned as a tumor suppressor to modulate the IL6/STAT3 signaling pathway. In summary, this study highlights the significant role of miR- 1301/STAT3 axis in CRC metastasis.

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Diethyldithiocarbamate-copper complex (CuET) inhibits colorectal cancer progression via miR-16-5p and 15b-5p/ALDH1A3/PKM2 axis-mediated aerobic glycolysis pathway

Oncogenesis ◽

10.1038/s41389-020-00295-7 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Xin Huang ◽

Yichao Hou ◽

Xiaoling Weng ◽

Wenjing Pang ◽

Lidan Hou ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

Copper Complex ◽

Aerobic Glycolysis ◽

Active Role ◽

Downstream Effector ◽

Glycolysis Pathway ◽

Colorectal Cancer Progression

AbstractExploring novel anticancer drugs to optimize the efficacy may provide a benefit for the treatment of colorectal cancer (CRC). Disulfiram (DSF), as an antialcoholism drug, is metabolized into diethyldithiocarbamate-copper complex (CuET) in vivo, which has been reported to exert the anticancer effects on various tumors in preclinical studies. However, little is known about whether CuET plays an anti-cancer role in CRC. In this study, we found that CuET had a marked effect on suppressing CRC progression both in vitro and in vivo by reducing glucose metabolism. Mechanistically, using RNA-seq analysis, we identified ALDH1A3 as a target gene of CuET, which promoted cell viability and the capacity of clonal formation and inhibited apoptosis in CRC cells. MicroRNA (miR)-16-5p and 15b-5p were shown to synergistically regulate ALDH1A3, which was negatively correlated with both of them and inversely correlated with the survival of CRC patients. Notably, using co-immunoprecipitation followed with mass spectrometry assays, we identified PKM2 as a direct downstream effector of ALDH1A3 that stabilized PKM2 by reducing ubiquitination. Taken together, we disclose that CuET treatment plays an active role in inhibiting CRC progression via miR-16-5p and 15b-5p/ALDH1A3/PKM2 axis–mediated aerobic glycolysis pathway.

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LAT1 and ASCT2 Related microRNAs as Potential New Therapeutic Agents against Colorectal Cancer Progression

Biomedicines ◽

10.3390/biomedicines9020195 ◽

2021 ◽

Vol 9 (2) ◽

pp. 195

Author(s):

Francisca Dias ◽

Cristina Almeida ◽

Ana Luísa Teixeira ◽

Mariana Morais ◽

Rui Medeiros

Keyword(s):

Colorectal Cancer ◽

Amino Acid ◽

Cancer Progression ◽

Cell Metabolism ◽

Tumor Development ◽

Amino Acid Transporters ◽

Epigenetic Alterations ◽

Therapeutic Approaches ◽

Colorectal Cancer Progression ◽

Made In

The development and progression of colorectal cancer (CRC) have been associated with genetic and epigenetic alterations and more recently with changes in cell metabolism. Amino acid transporters are key players in tumor development, and it is described that tumor cells upregulate some AA transporters in order to support the increased amino acid (AA) intake to sustain the tumor additional needs for tumor growth and proliferation through the activation of several signaling pathways. LAT1 and ASCT2 are two AA transporters involved in the regulation of the mTOR pathway that has been reported as upregulated in CRC. Some attempts have been made in order to develop therapeutic approaches to target these AA transporters, however none have reached the clinical setting so far. MiRNA-based therapies have been gaining increasing attention from pharmaceutical companies and now several miRNA-based drugs are currently in clinical trials with promising results. In this review we combine a bioinformatic approach with a literature review in order to identify a miRNA profile with the potential to target both LAT1 and ASCT2 with potential to be used as a therapeutic approach against CRC.

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