Implication of Different Tumor Biomarkers in Drug Resistance and Invasiveness in Primary and Metastatic Colorectal Cancer Cell Lines

Sánchez‐Díez, Marta; Alegría‐Aravena, Nicolás; López-Montes, Marta; Quiroz‐Troncoso, Josefa; González‐Martos, Raquel; Menéndez‐Rey, Adrián; Sánchez-Sánchez, José; Pastor, M.; Ramírez-Castillejo, Carmen

doi:10.3390/biomedicines10051083

Cited by 9 publications

(7 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This data correlates with previous data from other research groups which connect chemoresistance, tumourigenicity potential, and slow-cycling in some tumour cells [44,46,54]. Several other markers (such as TROP2) could be involved in this chemorresistance process too, as has been recently identi ed by our group [55].…”

Section: Discussionsupporting

confidence: 92%

Moonlight role of PEDF in breast cancer: self-renewal inhibition in breast cancer stem cells

Gil-Gas,

Sánchez-Díez,

Honrubia-Gómez

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Breast cancer is the leading cause of death among females in developed countries. Although the implementation of screening tests and the development of new therapies has increased the probability of remission, relapse rates remain high. Numerous studies have indicated the connection between cancer initiating cells and slow cellular cycle cells, identified by their capacity to retain long labelling (LT+). Methods: In this study, we perform tumour cell culture dose-response assays in adherent and mamospheres cultures. We also probe our conclusion in Xenograft models. Cell culture and in vivo tumours were analysed by immunofluorescence, qPCR and flow cytometry assays showing how stem cell self-renewal modulating proteins, such as PEDF, can statistically significant modify the properties, cell-percentage expressing biomarkers, and carcinogenicity of cancer stem cells (by student t-test). Results: The PEDF signaling pathway could be a useful tool for controlling cancer stem cells’ self-renewal, and therefore control patient relapse, as PEDF enhances resistance in breast cancer patient cells in vitro culture. We have designed a peptide consisting in the C-terminal part of this protein, which acts by blocking endogenous PEDF in culture cell assays. Conclusion: We demonstrate that it is possible to interfere with the self-renewal capacity of cancer stem cells, induce anoikis in vivo, and reduce resistance against Docetaxel treatment in cancer patient cells in in vitro culture. We have also demonstrated that this PEDF-modified protein produces a significant decrease in the percentage of cancer stem cell expressing markers.

show abstract

Section: Discussionsupporting

confidence: 92%

Moonlight role of PEDF in breast cancer: self-renewal inhibition in breast cancer stem cells

Gil-Gas,

Sánchez-Díez,

Honrubia-Gómez

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Finally, the relationship between TROP2 expression and resistance to oxaliplatin has been described in some CRC cells. It was suggested that the resistance was related to the TROP2-mediated enhancement of EpCAM-induced cell signaling [ 36 ].…”

Section: Introductionmentioning

confidence: 99%

TROP2 Represents a Negative Prognostic Factor in Colorectal Adenocarcinoma and Its Expression Is Associated with Features of Epithelial–Mesenchymal Transition and Invasiveness

Švec

Šťastná

Janečková

et al. 2022

Cancers

View full text Add to dashboard Cite

Trophoblastic cell surface antigen 2 (TROP2) is a membrane glycoprotein overexpressed in many solid tumors with a poor prognosis, including intestinal neoplasms. In our study, we show that TROP2 is expressed in preneoplastic lesions, and its expression is maintained in most colorectal cancers (CRC). High TROP2 positivity correlated with lymph node metastases and poor tumor differentiation and was a negative prognostic factor. To investigate the role of TROP2 in intestinal tumors, we analyzed two mouse models with conditional disruption of the adenomatous polyposis coli (Apc) tumor-suppressor gene, human adenocarcinoma samples, patient-derived organoids, and TROP2-deficient tumor cells. We found that Trop2 is produced early after Apc inactivation and its expression is associated with the transcription of genes involved in epithelial–mesenchymal transition, the regulation of migration, invasiveness, and extracellular matrix remodeling. A functionally similar group of genes was also enriched in TROP2-positive cells from human CRC samples. To decipher the driving mechanism of TROP2 expression, we analyzed its promoter. In human cells, this promoter was activated by β-catenin and additionally by the Yes1-associated transcriptional regulator (YAP). The regulation of TROP2 expression by active YAP was verified by YAP knockdown in CRC cells. Our results suggest a possible link between aberrantly activated Wnt/β-catenin signaling, YAP, and TROP2 expression.

show abstract

“…Many genes have been identified as potential inducers of epithelial-to-mesenchymal transition (EMT) in the progression of CC [ 29 , 30 ]. SSX2 expression was significantly higher in CC tissue samples with high disease grades than in NC tissue samples, suggesting that its expression is associated with cancer growth and metastasis.…”

Section: Discussionmentioning

confidence: 99%

Higher Expression Levels of SSX1 and SSX2 in Patients with Colon Cancer: Regulated In Vitro by the Inhibition of Methylation and Histone Deacetylation

et al. 2023

View full text Add to dashboard Cite

Background and Objectives: Colon cancer (CC) has a high mortality rate and is often diagnosed at an advanced stage in Saudi Arabia. Thus, the identification and characterization of potential new cancer-specific biomarkers are imperative for improving the diagnosis of CC by detecting it at an early stage. Cancer-testis (CT) genes have been identified as potential biomarkers for the early diagnosis of various cancers. Among the CT genes are those belonging to the SSX family. In order to assess the usefulness of SSX family genes as cancer biomarkers for the detection of early-stage CC, the goal of this research was to validate the expressions of these genes in patients with CC and in matched patients with normal colons (NCs). Materials and Methods: RT-PCR assays were used to analyze the SSX1, SSX2, and SSX3 family gene expression levels in 30 neighboring NC and CC tissue samples from male Saudi patients. Epigenetic alterations were also tested in vitro using qRT-PCR analysis to determine whether reduced DNA methyltransferase or histone deacetylation could stimulate SSX gene expression via 5-aza-2′-deoxycytidine and trichostatin treatments, respectively. Results: The RT-PCR results showed SSX1 and SSX2 gene expression in 10% and 20% of the CC tissue specimens, respectively, but not in any of the NC tissue specimens. However, no SSX3 expression was detected in any of the examined CC or NC tissue samples. In addition, the qRT-PCR results showed significantly higher SSX1 and SSX2 expression levels in the CC tissue samples than in the NC tissue samples. The 5-aza-2′-deoxycytidine and trichostatin treatments significantly induced the mRNA expression levels of the SSX1, SSX2, and SSX3 genes in the CC cells in vitro. Conclusions: These findings suggest that SSX1 and SSX2 are potentially suitable candidate biomarkers for CC. Their expressions can be regulated via hypomethylating and histone deacetylase treatments, subsequently providing a potential therapeutic target for CC.

show abstract

Implication of Different Tumor Biomarkers in Drug Resistance and Invasiveness in Primary and Metastatic Colorectal Cancer Cell Lines

Cited by 9 publications

References 64 publications

Moonlight role of PEDF in breast cancer: self-renewal inhibition in breast cancer stem cells

Moonlight role of PEDF in breast cancer: self-renewal inhibition in breast cancer stem cells

TROP2 Represents a Negative Prognostic Factor in Colorectal Adenocarcinoma and Its Expression Is Associated with Features of Epithelial–Mesenchymal Transition and Invasiveness

Higher Expression Levels of SSX1 and SSX2 in Patients with Colon Cancer: Regulated In Vitro by the Inhibition of Methylation and Histone Deacetylation

Contact Info

Product

Resources

About