scholarly journals Desmoplastic Reaction in Biopsy Specimens of T1 Stage Colorectal Cancer Plays a Critical Role in Defining the Level of Sub-Mucosal Invasion

10.5772/53451 ◽  
2013 ◽  
Author(s):  
Shigeki Tomita ◽  
Kazuhito Ichikawa ◽  
Takahiro Fujimori
Keyword(s):  
Colorectal Cancer ◽  
Critical Role ◽  
Desmoplastic Reaction ◽  
Biopsy Specimens ◽  
T1 Stage

Desmoplastic reaction in biopsy specimens of early colorectal cancer: A Japanese prospective multicenter study

2012 ◽  
Vol 62 (8) ◽  
pp. 525-531 ◽  
Author(s):  
Ryusuke Kimura ◽  
Takahiro Fujimori ◽  
Kazuhito Ichikawa ◽  
Yoichi Ajioka ◽  
Hideki Ueno ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Multicenter Study ◽  
Early Colorectal Cancer ◽  
Prospective Multicenter Study ◽  
Desmoplastic Reaction ◽  
Biopsy Specimens

The Critical Role of the miR-21-MEG2 Axis in Colorectal Cancer

2020 ◽  
Vol 30 (6) ◽  
pp. 509-518
Author(s):  
Zengtao Bao ◽  
Shanting Gao ◽  
Baoming Zhang ◽  
Wenchao Shi ◽  
Aimin Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Critical Role

scholarly journals RNF141 interacts with KRAS to promote colorectal cancer progression

Oncogene ◽  
2021 ◽  
Author(s):  
Jiuna Zhang ◽  
Xiaoyu Jiang ◽  
Jie Yin ◽  
Shiying Dou ◽  
Xiaoli Xie ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Plasma Membrane ◽  
Tumor Growth ◽  
Cancer Progression ◽  
Critical Role ◽  
Ring Finger ◽  
Immunohistochemical Analysis ◽  
Bimolecular Fluorescence Complementation

AbstractRING finger proteins (RNFs) play a critical role in cancer initiation and progression. RNF141 is a member of RNFs family; however, its clinical significance, roles, and mechanism in colorectal cancer (CRC) remain poorly understood. Here, we examined the expression of RNF141 in 64 pairs of CRC and adjacent normal tissues by real-time PCR, Western blot, and immunohistochemical analysis. We found that there was more expression of RNF141 in CRC tissue compared with its adjacent normal tissue and high RNF141 expression associated with T stage. In vivo and in vitro functional experiments were conducted and revealed the oncogenic role of RNF141 in CRC. RNF141 knockdown suppressed proliferation, arrested the cell cycle in the G1 phase, inhibited migration, invasion and HUVEC tube formation but promoted apoptosis, whereas RNF141 overexpression exerted the opposite effects in CRC cells. The subcutaneous xenograft models showed that RNF141 knockdown reduced tumor growth, but its overexpression promoted tumor growth. Mechanistically, liquid chromatography-tandem mass spectrometry indicated RNF141 interacted with KRAS, which was confirmed by Co-immunoprecipitation, Immunofluorescence assay. Further analysis with bimolecular fluorescence complementation (BiFC) and Glutathione-S-transferase (GST) pull-down assays showed that RNF141 could directly bind to KRAS. Importantly, the upregulation of RNF141 increased GTP-bound KRAS, but its knockdown resulted in a reduction accordingly. Next, we demonstrated that RNF141 induced KRAS activation via increasing its enrichment on the plasma membrane not altering total KRAS expression, which was facilitated by the interaction with LYPLA1. Moreover, KRAS silencing partially abolished the effect of RNF141 on cell proliferation and apoptosis. In addition, our findings presented that RNF141 functioned as an oncogene by upregulating KRAS activity in a manner of promoting KRAS enrichment on the plasma membrane in CRC.

scholarly journals Colorectal Cancer Apoptosis Induced by Dietary δ-Valerobetaine Involves PINK1/Parkin Dependent-Mitophagy and SIRT3

2021 ◽  
Vol 22 (15) ◽  
pp. 8117
Author(s):  
Nunzia D’Onofrio ◽  
Elisa Martino ◽  
Luigi Mele ◽  
Antonino Colloca ◽  
Martina Maione ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Current Knowledge ◽  
Apoptotic Cell ◽  
Critical Role ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Protein Levels

Understanding the mechanisms of colorectal cancer progression is crucial in the setting of strategies for its prevention. δ-Valerobetaine (δVB) is an emerging dietary metabolite showing cytotoxic activity in colon cancer cells via autophagy and apoptosis. Here, we aimed to deepen current knowledge on the mechanism of δVB-induced colon cancer cell death by investigating the apoptotic cascade in colorectal adenocarcinoma SW480 and SW620 cells and evaluating the molecular players of mitochondrial dysfunction. Results indicated that δVB reduced cell viability in a time-dependent manner, reaching IC50 after 72 h of incubation with δVB 1.5 mM, and caused a G2/M cell cycle arrest with upregulation of cyclin A and cyclin B protein levels. The increased apoptotic cell rate occurred via caspase-3 activation with a concomitant loss in mitochondrial membrane potential and SIRT3 downregulation. Functional studies indicated that δVB activated mitochondrial apoptosis through PINK1/Parkin pathways, as upregulation of PINK1, Parkin, and LC3B protein levels was observed (p < 0.0001). Together, these findings support a critical role of PINK1/Parkin-mediated mitophagy in mitochondrial dysfunction and apoptosis induced by δVB in SW480 and SW620 colon cancer cells.

scholarly journals MIR21-induced loss of junctional adhesion molecule A promotes activation of oncogenic pathways, progression and metastasis in colorectal cancer

2021 ◽  
Author(s):  
Andrea Lampis ◽  
Jens C. Hahne ◽  
Pierluigi Gasparini ◽  
Luciano Cascione ◽  
Somaieh Hedayat ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Critical Role ◽  
Tumour Volume ◽  
Cell Permeability ◽  
Oncogenic Pathways ◽  
Morphogenetic Protein ◽  
Cancer Phenotype ◽  
And Migration ◽  
2D And 3D

AbstractJunctional adhesion molecules (JAMs) play a critical role in cell permeability, polarity and migration. JAM-A, a key protein of the JAM family, is altered in a number of conditions including cancer; however, consequences of JAM-A dysregulation on carcinogenesis appear to be tissue dependent and organ dependent with significant implications for the use of JAM-A as a biomarker or therapeutic target. Here, we test the expression and prognostic role of JAM-A downregulation in primary and metastatic colorectal cancer (CRC) (n = 947). We show that JAM-A downregulation is observed in ~60% of CRC and correlates with poor outcome in four cohorts of stages II and III CRC (n = 1098). Using JAM-A knockdown, re-expression and rescue experiments in cell line monolayers, 3D spheroids, patient-derived organoids and xenotransplants, we demonstrate that JAM-A silencing promotes proliferation and migration in 2D and 3D cell models and increases tumour volume and metastases in vivo. Using gene-expression and proteomic analyses, we show that JAM-A downregulation results in the activation of ERK, AKT and ROCK pathways and leads to decreased bone morphogenetic protein 7 expression. We identify MIR21 upregulation as the cause of JAM-A downregulation and show that JAM-A rescue mitigates the effects of MIR21 overexpression on cancer phenotype. Our results identify a novel molecular loop involving MIR21 dysregulation, JAM-A silencing and activation of multiple oncogenic pathways in promoting invasiveness and metastasis in CRC.

scholarly journals Signaling pathways in intestinal homeostasis and colorectal cancer: KRAS at centre stage

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Camille Ternet ◽  
Christina Kiel
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathways ◽  
Intestinal Microbiota ◽  
Critical Role ◽  
Neuroendocrine Cells ◽  
Cell Junction ◽  
Intestinal Cell ◽  
Intestinal Homeostasis ◽  
Cell Functions ◽  
The Impact

AbstractThe intestinal epithelium acts as a physical barrier that separates the intestinal microbiota from the host and is critical for preserving intestinal homeostasis. The barrier is formed by tightly linked intestinal epithelial cells (IECs) (i.e. enterocytes, goblet cells, neuroendocrine cells, tuft cells, Paneth cells, and M cells), which constantly self-renew and shed. IECs also communicate with microbiota, coordinate innate and adaptive effector cell functions. In this review, we summarize the signaling pathways contributing to intestinal cell fates and homeostasis functions. We focus especially on intestinal stem cell proliferation, cell junction formation, remodelling, hypoxia, the impact of intestinal microbiota, the immune system, inflammation, and metabolism. Recognizing the critical role of KRAS mutants in colorectal cancer, we highlight the connections of KRAS signaling pathways in coordinating these functions. Furthermore, we review the impact of KRAS colorectal cancer mutants on pathway rewiring associated with disruption and dysfunction of the normal intestinal homeostasis. Given that KRAS is still considered undruggable and the development of treatments that directly target KRAS are unlikely, we discuss the suitability of targeting pathways downstream of KRAS as well as alterations of cell extrinsic/microenvironmental factors as possible targets for modulating signaling pathways in colorectal cancer.

scholarly journals Enteric Glia Play a Critical Role in Promoting the Development of Colorectal Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Robert Yuan ◽  
Nupur Bhattacharya ◽  
Justin A. Kenkel ◽  
Jeanne Shen ◽  
Michael A. DiMaio ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Critical Role ◽  
Enteric Glia

scholarly journals Novel Pathological Predictive Factors for Extranodal Extension in Oral Squamous Cell Carcinoma: a Retrospective Cohort Study Based on Tumor Budding, Desmoplastic Reaction, and Tumor-infiltrating Lymphocytes

2021 ◽  
Author(s):  
Yuri Noda ◽  
Mitsuaki Ishida ◽  
Yasuhiro Ueno ◽  
Takuo Fujisawa ◽  
Hiroshi Iwai ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Tumor Microenvironment ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumor Infiltrating Lymphocytes ◽  
Desmoplastic Reaction ◽  
Extranodal Extension ◽  
Biopsy Specimens ◽  
Infiltrating Lymphocytes

Abstract Background: Extranodal extension (ENE) is a poor prognostic factor for oral squamous cell carcinoma (OSCC). Identifying ENE by clinical and/or radiological examination is difficult, thereby leading to unnecessary neck dissections. Currently, no definitive predictors are available for ENE. Thus, we aimed to determine the histological predictors of ENE by routine histopathological examination using biopsy and surgically resected specimens.Methods: This retrospective study included 186 surgically resected OSCC and 83 matched biopsy specimens. Clinical features associated with the tumor microenvironment, including desmoplastic reaction (DR), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs), were evaluated using hematoxylin and eosin-stained primary OSCC and neck dissection specimens. These histological features were divided into two groups: DR-immature (DR-I) and DR-mature (DR-M); TB-high (TB-H) and TB-low (TB-L); and TILs-low (TILs-L) and TILs-high (TILs-H). Clinical depth of invasion (cDOI) and pathological DOI (pDOI) were adapted for biopsies and resections, respectively; DOI was evaluated as DOI >10 mm and DOI ≤10 mm. The clinicopathological relationships between these histopathological features and ENE and the independent risk factors for ENE were analyzed. The histological predictors of ENE were evaluated.Results:The histological status of DR, TILs, and TB present in biopsy and resection specimens showed high accuracy with that of ENE. DR-I, TILs-L, and TB-H were significantly associated with lymph node metastasis, cDOI, and pDOI. Bivariate and multivariate analyses revealed that TB-H and pDOI >10 mm in resections were independent factors for the presence of ENE (ENE+). The combination of TB-H/pDOI >10 mm in resection specimens showed high specificity (91%) and accuracy (83%) regarding ENE+. Although there proved to be no independent factors in biopsies, DR-I and TILs-L were significantly associated with ENE+ (p<0.001). The combination of DR-I/TILs-L/cDOI >10 mm in biopsies exhibited high sensitivity and specificity with ENE+ (70% and 77%, respectively, p<0.001). These histological predictors could detect even minor ENE (<2 mm).Conclusions:The tumor microenvironment status in primary OSCC was significantly associated with that of ENE, and TB-H was an independent risk factor for ENE. The histological status of DR-I/TILs-L/cDOI >10 mm in biopsy specimens and TB-H/pDOI >10 mm in resection specimens is a useful predictor of ENE.

scholarly journals Urinary 8-iso PGF2α and 2,3-dinor-8-iso PGF2α can be indexes of colitis-associated colorectal cancer in mice

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245292
Author(s):  
Yusuke Miyazaki ◽  
Tatsuro Nakamura ◽  
Shinya Takenouchi ◽  
Akane Hayashi ◽  
Keisuke Omori ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Morphological Study ◽  
Critical Role ◽  
Repeated Administration ◽  
Tumor Formation ◽  
Liquid Chromatography Mass Spectrometry ◽  
Chromatography Mass Spectrometry ◽  
Lipid Metabolites

Early diagnosis of colorectal cancer is needed to reduce the mortal consequence by cancer. Lipid mediators play critical role in progression of colitis and colitis-associated colon cancer (CAC) and some of their metabolites are excreted in urine. Here, we attempted to find novel biomarkers in urinary lipid metabolite of a murine model of CAC. Mice were received single administration of azoxymethane (AOM) and repeated administration of dextran sulfate sodium (DSS). Lipid metabolites in their urine was measured by liquid chromatography mass spectrometry and their colon was collected to perform morphological study. AOM and DSS caused inflammation and tumor formation in mouse colon. Liquid chromatography mass spectrometry-based comprehensive analysis of lipid metabolites showed that cyclooxygenase-mediated arachidonic acid (AA) metabolites, prostaglandins, and reactive oxygen species (ROS)-mediated AA metabolites, isoprostanes, were predominantly increased in the urine of tumor-bearing mice. Among that, urinary prostaglandin (PG)E2 metabolite tetranor-PGEM and PGD2 metabolite tetranor-PGDM were significantly increased in both of urine collected at the acute phase of colitis and the carcinogenesis phase. On the other hand, two F2 isoprostanes (F2-IsoPs), 8-iso PGF2α and 2,3-dinor-8-iso PGF2α, were significantly increased only in the carcinogenesis phase. Morphological study showed that infiltrated monocytes into tumor mass strongly expressed ROS generator NADPH (p22phox). These observations suggest that urinary 8-iso PGF2α and 2,3-dinor-8-iso PGF2α can be indexes of CAC.

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