Clinico-Pathological Correlation of β-Catenin and Telomere Dysfunction in Head and Neck Squamous Cell Carcinoma Patients

Padhi, Swatishree; Saha, Arka; Kar, Madhabananda; Ghosh, Chinmoy; Adhya, Amit Kumar; Baisakh, Manas; Mohapatra, Nachiketa; Somasundaram, Venkatesan; Hande, M. Prakash; Banerjee, Birendranath

doi:10.7150/jca.9558

Cited by 32 publications

(30 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Beside hematological malignancies, a contribution of dysregulated Wnt signaling was also demonstrated for oral squamous cell cancer (OSCC) and aberrant accumulation of β-cat seems to support invasion and migration of OSCC cells, at least in vitro (see [11] and references therein). In accordance, Padhi et al reported of a correlation between β-cat expression and poor prognosis in head and neck cancer [12] in vivo . This is supported by the very recent finding that inactivation of several Wnt inhibitors through methylation is frequently found in oral cancer, correlating with a shorter survival [13].…”

Section: Introductionsupporting

confidence: 76%

The anti-apoptotic PON2 protein is Wnt/β-catenin-regulated and correlates with radiotherapy resistance in OSCC patients

et al. 2016

View full text Add to dashboard Cite

Aberrant Wnt signaling and control of anti-apoptotic mechanisms are pivotal features in different types of cancer to undergo cell death programs. The intracellular human enzyme Paraoxonase-2 (PON2) is known to have anti-apoptotic properties in leukemia and oral squamous cell cancer (OSCC) cells. However, the distinct regulating pathways are poorly understood. First, we present a so far unknown regulation of PON2 protein expression through the Wnt/GSK3β/β-catenin pathway in leukemia and OSCC cells. This was confirmed via in silico analysis, promoter reporter studies and treatment of multiple cell lines (K562, SCC-4, PCI-13) with different Wnt ligands/inhibitors in vitro. Ex vivo analysis of OSCC patients revealed a correlation between PON2 and β-catenin expression in tumor tissue. Higher PON2 expression in OSCC is associated with relapse independently of treatment (e.g. surgery/radio-/chemotherapy). These results emphasize the clinical impact of the newly described regulation of PON2 through Wnt/GSK3β/β-catenin. More importantly, the study revealed the fundamental finding of an overall Wnt/GSK3β/β-catenin dependent regulation of PON2 in different cancers, which was confirmed by systematic and multimethodological approaches. Thus, the herein presented mechanistic insight contributes to a better understanding of tumor specific escape from cell death strategies and suggests PON2 as a new potential biomarker for therapy resistance or as a prognostic tumor marker.

show abstract

Section: Introductionsupporting

confidence: 76%

The anti-apoptotic PON2 protein is Wnt/β-catenin-regulated and correlates with radiotherapy resistance in OSCC patients

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Previously we reported importance of β-catenin in prognosis of oral cancer and its overexpression in clonospheres along with hTERT and TRF2 [20,22]. In the present study, we observed a significant overexpression of β-catenin, TRF2 and hTERT at 40µM concentration and low expression was observed at 80µM concentrations compared to the untreated control (p<0.001) in parental HCT-116 (Fig 2e).…”

Section: Discussionsupporting

confidence: 62%

“…A significant population of cells was observed to efflux Hoechst 33342 dye when treated with increasing concentration of Bleomycin (20,40, 60, 80 μM) (Fig 1a and 1b). This small subpopulation of cells called Side Population (SP) increased with increasing concentration and then stabilized to a uniform percentage at higher concentrations.…”

Section: Prevalence Of a Side-population Of Cells With Stem Cell Likementioning

confidence: 97%

“…Mean γH2Ax foci/nuclei was observed to significantly increase (p<0.05) with increasing concentrations of Bleomycin (20,40, 60, 80 μM) in parental HCT-116 (Fig 1e and 1f). Increased foci are indicative of increasing DNA damage.…”

Section: Increasing Dna Damage As Seen Through γH2ax Immunocytochemismentioning

confidence: 98%

“…Real time PCR was performed by laboratory established protocol as described previously [20]. Primers used are mentioned in Table 1.…”

Section: Real Time Pcrmentioning

confidence: 99%

See 2 more Smart Citations

Role of TRF2 in efficient DNA repair, spheroid formation and Cancer Stem Cell maintenance

Saha¹,

Padhi²,

Kar³

et al. 2017

Oncomedicine

Self Cite

View full text Add to dashboard Cite

Chemotherapeutic resistance post-surgical management may be linked to an efficient DNA repair mechanism and survival of cancer stem cells. We report the presence of cancer stem cell like Side Population and their survival and enrichment post treatment with bleomycin in HCT116 cell line. The Side Population exhibited spheroidal characteristics and efficient repair of DNA damage foci compared to the parental HCT-116 cells. We report upregulated expression of β-catenin, TRF2, hTERT, CD44, CD24 and Oct4 genes in parental and clonospheres in a DNA damage environment. Comparative gene expression studies of parental and clonospheric HCT-116 cells revealed significant upregulation (p<0.01) of TRF2 gene in clonospheres. TRF2 which is a Telomere shelterin component is mainly involved in telomere maintenance and DNA repair. We report a role of TRF2 in cancer stem cell maintenance and efficient DNA repair in the clonospheric sub-population of HCT 116 cell line. Silencing of TRF2 gene significantly downregulated β-catenin, CD44, CD24, Oct4 and reduced the size of the clonospheres (4.448μm) when compared to scrambled non-silenced control (11.7273μm). TRF2 Silenced HCT116 parental cells reported compromised DNA repair and 2-fold increase in the number of DSBs as well as γH2Ax foci in the presence of a DSB generating agent Bleomycin, when compared to scrambled non-silenced control. In this study, we confirm a definitive role of TRF2 in stemness of cancer cells and DNA damage response and repair which is an extra-telomeric function and may have therapeutic implications in management of tumor recurrence.

show abstract

RETRACTED: CUL4B promotes aggressive phenotypes of HNSCC via the activation of the Wnt/β‐catenin signaling pathway

Wang

Yue

2019

Cancer Medicine

View full text Add to dashboard Cite

Previous studies have revealed that CUL4B is overexpressed in various types of cancer and that its overexpression is related to the progression and metastasis of tumors. However, the biological functions of CUL4B in the progression of head and neck squamous cell carcinoma (HNSCC) are still not well understood. In the current study, we aimed to determine the changes in biological functions and molecular events that are related to CUL4B overexpression. Interestingly, our results showed that CUL4B is upregulated in HNSCC and that its upregulation is associated with poor survival and worse histological grade. Overexpression of CUL4B promoted cancer cell growth, invasion, and migration, as well as epithelial‐mesenchymal transition, whereas the loss of CUL4B abrogated these malignant phenotypes. Moreover, our mechanistic investigations suggest that the Wnt/β‐catenin signaling pathway was activated by CUL4B overexpression. Treatment with a Wnt/β‐catenin inhibitor decreased CUL4B‐induced migration and invasion, establishing a key role of Wnt/β‐catenin signaling in mediating the effects of CUL4B expression. Together, these results demonstrate a key contribution of CUL4B overexpression in the malignant behavior of HNSCC cells, at least in part through the stimulation of angiogenesis and the activation of the Wnt/β‐catenin signaling pathway.

show abstract

Clinico-Pathological Correlation of β-Catenin and Telomere Dysfunction in Head and Neck Squamous Cell Carcinoma Patients

Cited by 32 publications

References 42 publications

The anti-apoptotic PON2 protein is Wnt/β-catenin-regulated and correlates with radiotherapy resistance in OSCC patients

The anti-apoptotic PON2 protein is Wnt/β-catenin-regulated and correlates with radiotherapy resistance in OSCC patients

Role of TRF2 in efficient DNA repair, spheroid formation and Cancer Stem Cell maintenance

RETRACTED: CUL4B promotes aggressive phenotypes of HNSCC via the activation of the Wnt/β‐catenin signaling pathway

Contact Info

Product

Resources

About