Tenascin-C predicts poor outcomes for patients with colorectal cancer and drives cancer stemness via Hedgehog signaling pathway

Yang, Zheng; Zhang, Chengye; Feng, Ying; Quan, Mingji; Cui, Yan; Xuan, Yanhua

doi:10.1186/s12935-020-01188-w

Cited by 17 publications

(18 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Aberrant activation of the Hh signaling pathway is associated with tumorigenesis in various tissues, and most studies specify that the Hedgehog signaling pathway participates in the oncogenesis of CRC [26]. Some oncogenes promote the stemness and drug resistance of CRC by aberrant activation of the Hedgehog signaling pathway [27][28][29][30].…”

Section: Discussionmentioning

confidence: 99%

RUNX1 regulates the proliferation and chemoresistance of colorectal cancer through the Hedgehog signaling pathway

Li¹,

Lai²,

He³

et al. 2021

J. Cancer

View full text Add to dashboard Cite

Background: Chemoresistance is one of the main causes of recurrence in colorectal cancer (CRC) patients and leads to a poor prognosis. To characterize RUNX1 expression in colorectal cancer (CRC) and elucidate its mechanistic involvement in the tumor biology of this disease. Methods: The expression of RUNX1 in CRC and normal tissues was detected by bioinformatics analysis. Cell proliferation was measured by CCK-8 and clonogenic assays. In vivo tumor progression was assessed with a xenograft mouse model. Cell drug sensitivity tests and flow cytometry were performed to analyze CRC cell chemoresistance. RUNX1, key molecules of the Hedgehog signaling pathway, and ABCG2 were detected by qRT-PCR and Western blotting. Results: RUNX1 expression is upregulated in CRC tissues. RUNX1 enhanced CRC cell resistance to 5-fluorouracil (5-FU), promoted proliferation, and inhibited 5-FU-induced apoptosis. Mechanistically, RUNX1 can activate the Hedgehog signaling pathway and promote the expression of ABCG2 in CRC cells. Conclusions: Our study demonstrated that RUNX1 promotes CRC proliferation and chemoresistance by activating the Hedgehog signaling pathway and ABCG2 expression.

show abstract

Section: Discussionmentioning

confidence: 99%

RUNX1 regulates the proliferation and chemoresistance of colorectal cancer through the Hedgehog signaling pathway

Li¹,

Lai²,

He³

et al. 2021

J. Cancer

View full text Add to dashboard Cite

show abstract

“…In summary, we revealed an overexpression of ECM components, which are associated with enhanced migratory capacities of tumour cells ( TNC [ 76 , 77 ], FN1 [ 78 ]), resistance to chemotherapy ( COL11A1 [ 43 , 75 ], SPP1 [ 79 ]) and adverse outcome ( COL11A1 [ 42 ], TNC [ 80 ], FN1 [ 78 ]) in other primaries. The functional role of these molecules and their potential as therapeutic targets are currently under intense investigation [ 65 , 66 , 75 , 79 , 81 , 82 ].…”

Section: Discussionmentioning

confidence: 99%

Expression Profiling of Extracellular Matrix Genes Reveals Global and Entity-Specific Characteristics in Adenoid Cystic, Mucoepidermoid and Salivary Duct Carcinomas

Arolt

Meyer

Hoffmann

et al. 2020

Cancers

View full text Add to dashboard Cite

The composition of the extracellular matrix (ECM) plays a pivotal role in tumour initiation, metastasis and therapy resistance. Until now, the ECM composition of salivary gland carcinomas (SGC) has not been studied. We quantitatively analysed the mRNA of 28 ECM-related genes of 34 adenoid cystic (AdCy; n = 11), mucoepidermoid (MuEp; n = 14) and salivary duct carcinomas (SaDu; n = 9). An incremental overexpression of six collagens (including COL11A1) and four glycoproteins from MuEp and SaDu suggested a common ECM alteration. Conversely, AdCy and MuEp displayed a distinct overexpression of COL27A1 and LAMB3, respectively. Nonhierarchical clustering and principal component analysis revealed a more specific pattern for AdCy with low expression of the common gene signature. In situ studies at the RNA and protein level confirmed these results and indicated that, in contrast to MuEp and SaDu, ECM production in AdCy results from tumour cells and not from cancer-associated fibroblasts (CAFs). Our findings reveal different modes of ECM production leading to common and distinct RNA signatures in SGC. Of note, an overexpression of COL27A1, as in AdCy, has not been linked to any other neoplasm so far. Here, we contribute to the dissection of the ECM composition in SGC and identified a panel of deferentially expressed genes, which could be putative targets for SGC therapy and overcoming therapeutic resistance.

show abstract

“…TNC may be involved in cancer growth and metastatic processes via the Hedgehog (HH) signaling pathway, caused either by mutations in the pathway (ligand independent) or through HH overexpression (ligand dependent) [19]. HH signaling starts with secretion of the HH ligand, followed by secretion of Patched (PTC), the transmembrane protein Smoothened (SMO) and three GLI (Glioma-associated oncogene) zinc nger transcription factors [20].…”

Section: Discussionmentioning

confidence: 99%

Expression Patterns of Microenvironmental Factors and Tenascin-C at the Invasive Front of Stage II And III Colorectal Cancer: Novel Tumor Prognostic Markers

Hashimoto

Uesugi

Osaka

et al. 2021

Preprint

View full text Add to dashboard Cite

Background. Biological markers expressed in cancer cells and the surrounding cancer-associated fibroblasts (CAF) can be used for prediction of patient prognosis in colorectal cancer (CRC). Here, we used immunohistochemical techniques to evaluate cancer cells’ expression of specific biomarkers that are closely associated with neoplastic progression. Patients and Methods. Immunohistochemical markers included Ki-67, p53, β-catenin, MMP7, E-cadherin and HIF1-α. We also characterized microenvironmental markers expressed by CAF, including expression of α-smooth muscle actin, CD10, podoplanin, fibroblast specific protein 1, platelet derived growth factor β, fibroblast association protein, tenascin-C (TNC), ZEB1 and TWIST1. The study population consisted of 286 CRC patients with stage II and III disease. Stage II and III CRC were divided into a first and a second cohort (for validation). The CRCs were stratified using cluster analysis. To identify the utility of prognostic markers in stage II and III CRC, univariate and multivariate analyses were performed in both cohorts. Results. Stage II and III CRCs were stratified into 3 subgroups. Specific subgroups were significantly correlated to disease-free survival using univariate and multivariate analyses in the first cohort. High expression of TNC was identified as a single prognostic marker in both cohorts by univariate and multivariate analyses. Conclusions. We suggest that the presence of a specific subgroup defined by multiple markers can be used for prediction of CRC outcome in stages II and III. In addition, we showed that high expression of TNC was correlated with a poorer prognosis in stages II and III of CRC.

show abstract

Tenascin-C predicts poor outcomes for patients with colorectal cancer and drives cancer stemness via Hedgehog signaling pathway

Cited by 17 publications

References 18 publications

RUNX1 regulates the proliferation and chemoresistance of colorectal cancer through the Hedgehog signaling pathway

RUNX1 regulates the proliferation and chemoresistance of colorectal cancer through the Hedgehog signaling pathway

Expression Profiling of Extracellular Matrix Genes Reveals Global and Entity-Specific Characteristics in Adenoid Cystic, Mucoepidermoid and Salivary Duct Carcinomas

Expression Patterns of Microenvironmental Factors and Tenascin-C at the Invasive Front of Stage II And III Colorectal Cancer: Novel Tumor Prognostic Markers

Contact Info

Product

Resources

About