SOX9 expression predicts relapse of stage II colon cancer patients

Espersen, Maiken Lise Marcker; Linnemann, Dorte; Christensen, Ib Jarle; Alamili, Mahdi; Troelsen, Jesper T.; Høgdall, Estrid

doi:10.1016/j.humpath.2015.12.026

Cited by 23 publications

(34 citation statements)

References 36 publications

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“…This also explains why despite SOX9 being a target of the Wnt/ß-catenin pathway [1] and consequently, is highly expressed in CRC compared to adjacent healthy tissues [9], SOX9 expression level was shown not to provide prognostic values and high levels of SOX9 cannot be considered as a biomarker [29]. Inversely, low levels of SOX9 at the invasive front of the primary tumor have even been shown to be an independent predictor of relapse in stage II colon cancer patients [30]. In addition, SOX9 mutations are frequent in CRC [8] and according to ICGC (http://dcc.icgc.org/web/), the Sox9 gene is in the top 20 mutated genes with high functional impact.…”

Section: Discussionmentioning

confidence: 99%

SOX9 is an atypical intestinal tumor suppressor controlling the oncogenic Wnt/ß-catenin signaling

et al. 2016

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SOX9 inactivation is frequent in colorectal cancer (CRC) due to SOX9 gene mutations and/or to ectopic expression of MiniSOX9, a dominant negative inhibitor of SOX9. In the present study, we report a heterozygous L142P inactivating mutation of SOX9 in the DLD-1 CRC cell line and we demonstrate that the conditional expression of a wild type SOX9 in this cell line inhibits cell growth, clonal capacity and colonosphere formation while decreasing both the activity of the oncogenic Wnt/ß-catenin signaling pathway and the expression of the c-myc oncogene. This activity does not require SOX9 transcriptional function but, rather, involves an interaction of SOX9 with nuclear ß-catenin. Furthermore, we report that SOX9 inhibits tumor development when conditionally expressed in CRC cells injected either subcutaneous or intraperitoneous in BALB/c mice as an abdominal metastasis model. These observations argue in favor of a tumor suppressor activity for SOX9. As an siRNA targeting SOX9 paradoxically also inhibits DLD-1 and HCT116 CRC cell growth, we conclude that there is a critical level of endogenous active SOX9 needed to maintain CRC cell growth.

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Section: Discussionmentioning

confidence: 99%

SOX9 is an atypical intestinal tumor suppressor controlling the oncogenic Wnt/ß-catenin signaling

et al. 2016

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“…The enrollment, exclusion, and characteristics of patients in this retrospective study cohort have been described in a previously published paper (15). Briefly, the patient cohort included primary tumors from 144 patients diagnosed and treated for primary stage II colon cancer at Glostrup University Hospital, Gentofte University Hospital, and Herlev University Hospital, Denmark.…”

Section: Patient Cohortmentioning

confidence: 99%

“…Moreover, patients who relapsed within 3 months or died less than a month after primary surgery was excluded from the study. The MMR status of the primary tumor as well as histopathological risk factors, tumor location, age, and gender was registered as previously described (15).…”

Section: Patient Cohortmentioning

confidence: 99%

The prognostic value of polycomb group protein B‐cell‐specific moloney murine leukemia virus insertion site 1 in stage II colon cancer patients

Espersen

Linnemann

Christensen

et al. 2016

APMIS

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The aim of this study was to investigate the prognostic value of B-cell-specific moloney murine leukemia virus insertion site 1 (BMI1) protein expression in primary tumors of stage II colon cancer patients. BMI1 protein expression was assessed by immunohistochemistry in a retrospective patient cohort consisting of 144 stage II colon cancer patients. BMI1 expression at the invasive front of the primary tumors correlated with mismatch repair status of the tumors. Furthermore, BMI1 expression at the luminal surface correlated with T-stage, tumor location, and the histological subtypes of the tumors. In a univariate Cox proportional hazard analysis, no statistical significant association between risk of relapse and BMI1 protein expression at the invasive front (HR: 1.12; 95% CI 0.78-1.60; p = 0.53) or at the luminal surface of the tumor (HR: 1.06; 95% CI 0.75-1.48; p = 0.70) was found. Likewise, there was no association between 5-year overall survival and BMI1 expression at the invasive front (HR: 1.12; 95% CI 0.80-1.56; p = 0.46) or at the luminal surface of the tumor (HR: 1.16; 95% CI 0.86-1.60; p = 0.33). In conclusion, BMI1 expression in primary tumors of stage II colon cancer patients could not predict relapse or overall survival of the patients, thus having a limited prognostic value in stage II colon cancer patients.

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“…SOX9 acts a regulator of Wnt/beta-catenin pathway and a transcriptional target to maintain intestinal epithelium homeostasis [108]. In addition, SOX9 expression is an important biomarker for the prediction of colorectal cancer relapse [109]. MiR-145 also directly targets catenin δ-1 and contributes largely to oncogenic Wnt/beta-catenin signaling in human colon cancer cells (Figure 2) [104].…”

Section: Tumor Suppressor Genesmentioning

confidence: 99%

Potential roles of microRNAs and ROS in colorectal cancer: diagnostic biomarkers and therapeutic targets

Chuang

Zuo

2017

Oncotarget

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As one of the most commonly diagnosed cancers worldwide, colorectal adenocarcinoma often occurs sporadically in individuals aged 50 or above and there is an increase among younger patients under 50. Routine screenings are recommended for this age group to improve early detection. The multifactorial etiology of colorectal cancer consists of both genetic and epigenetic factors. Recently, studies have shown that the development and progression of colorectal cancer can be attributed to aberrant expression of microRNA. Reactive oxygen species (ROS) that play a key role in cancer cell survival, can also lead to carcinogenesis and cancer exacerbations. Given the rapid accumulating knowledge in the field, an updated review regarding microRNA and ROS in colorectal cancer is necessary. An extensive literature search has been conducted in PubMed/Medline databases to review the roles of microRNAs and ROS in colorectal cancer. Unique microRNA expression in tumor tissue, peripheral blood, and fecal samples from patients with colorectal cancer is outlined. Therapeutic approaches focusing on microRNA and ROS in colorectal cancer treatment is also delineated. This review aims to summarize the newest knowledge on the pathogenesis of colorectal cancer in the hopes of discovering novel diagnostic biomarkers and therapeutic techniques.

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SOX9 expression predicts relapse of stage II colon cancer patients

Cited by 23 publications

References 36 publications

SOX9 is an atypical intestinal tumor suppressor controlling the oncogenic Wnt/ß-catenin signaling

SOX9 is an atypical intestinal tumor suppressor controlling the oncogenic Wnt/ß-catenin signaling

The prognostic value of polycomb group protein B‐cell‐specific moloney murine leukemia virus insertion site 1 in stage II colon cancer patients

Potential roles of microRNAs and ROS in colorectal cancer: diagnostic biomarkers and therapeutic targets

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