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Comparison of the tumor size in the in vivo functional analysis of PODXL using PODXL-KO OSCC lines. (A) After euthanizing mice at day 21, tumors were resected. Scale bar = 1 cm. (B) Tumor weights were measured after tumor resection on day 21. The values are presented as mean ? SEM. Asterisks indicate statistical significance between HSC-2 and HSC-2/PODXL-KO cell lines (*P < 0.05, **P < 0.01, Tukey-Kramer's test).
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Oral cancers constitute approximately 2% of all cancers, with the most common histological type being oral squamous cell carcinoma (OSCC), representing 90% of oral cancers. Although diagnostic technologies and therapeutic techniques have progressed, the survival rate of patients with OSCC is still 60%, whereas the incidence rate has increased. Podo...
Contexts in source publication
Context 1
... day 21 after inoculation, all tumors were measured, following the resection of mice (Fig. 4A). As depicted in Fig. 4B, the tumor weight from HSC-2/PODXL-KO #1 and #2 cell lines were significantly lower than those from parental HSC-2 cell lines. The tumor weight from HSC- 2/PODXL-KO #3 was not significantly different from that of parental HSC-2 cell line (Fig. 4B), whereas the tumor volumes from HSC-2/ PODXL-KO #3 cell lines were significantly lower than those from par- ental HSC-2 cell lines (Fig. 3A). Hematoxylin and eosin staining of re- sected tumors of parental HSC-2, HSC-2/PODXL-KO #1, HSC-2/ PODXL-KO #2, and HSC-2/PODXL-KO #3 on day 21 are shown in Supplementary Fig. ...
Context 2
... day 21 after inoculation, all tumors were measured, following the resection of mice (Fig. 4A). As depicted in Fig. 4B, the tumor weight from HSC-2/PODXL-KO #1 and #2 cell lines were significantly lower than those from parental HSC-2 cell lines. The tumor weight from HSC- 2/PODXL-KO #3 was not significantly different from that of parental HSC-2 cell line (Fig. 4B), whereas the tumor volumes from HSC-2/ PODXL-KO #3 cell lines were significantly lower than those from par- ental HSC-2 cell lines (Fig. 3A). Hematoxylin and eosin staining of re- sected tumors of parental HSC-2, HSC-2/PODXL-KO #1, HSC-2/ PODXL-KO #2, and HSC-2/PODXL-KO #3 on day 21 are shown in Supplementary Fig. ...
Context 3
... day 21 after inoculation, all tumors were measured, following the resection of mice (Fig. 4A). As depicted in Fig. 4B, the tumor weight from HSC-2/PODXL-KO #1 and #2 cell lines were significantly lower than those from parental HSC-2 cell lines. The tumor weight from HSC- 2/PODXL-KO #3 was not significantly different from that of parental HSC-2 cell line (Fig. 4B), whereas the tumor volumes from HSC-2/ PODXL-KO #3 cell lines were significantly lower than those from par- ental HSC-2 cell lines (Fig. 3A). Hematoxylin and eosin staining of re- sected tumors of parental HSC-2, HSC-2/PODXL-KO #1, HSC-2/ PODXL-KO #2, and HSC-2/PODXL-KO #3 on day 21 are shown in Supplementary Fig. ...
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... PODXL is known to play a crucial role in maintaining adequate cellular infiltration because of its anti-adhesive properties; it can regulate cell adhesion by dissociating from actin, resulting in the loss of podocyte integrity [15][16][17]. PODXL has been reported to be overexpressed in a variety of malignancies, and strong cell-membrane expression has been associated with both tumor aggressiveness and poor prognoses in a variety of tumors, including CRC [18][19][20][21]. In addition, PODXL has been shown to act as an EMT mediator, to be involved in metastatic behavior, and to induce actin recruitment in several types of cancer cells [22][23][24]. ...
The primary cause of colorectal cancer (CRC) recurrence is increased distant metastasis after radiotherapy, so there is a need for targeted therapeutic approaches to reduce the metastatic-relapse risk. Dysregulation of the cell-surface glycoprotein podocalyxin-like protein (PODXL) plays an important role in promoting cancer-cell motility and is associated with poor prognoses for many malignancy types. We found that CRC cells exposed to radiation demonstrated increased TGFβ and PODXL expressions, resulting in increased migration and invasiveness due to increased extracellular matrix deposition. In addition, both TGFβ and PODXL were highly expressed in tissue samples from radiotherapy-treated CRC patients compared to those from patients without this treatment. However, it is unclear whether TGFβ and PODXL interactions are involved in cancer-progression resistance after radiation exposure in CRC. Here, using CRC cells, we showed that silencing PODXL blocked radiation-induced cell migration and invasiveness. Cell treatment with galunisertib (a TGFβ-pathway inhibitor) also led to reduced viability and migration, suggesting that its clinical use may enhance the cytotoxic effects of radiation and lead to the effective inhibition of CRC progression. Overall, the results demonstrate that downregulation of TGFβ and its-mediated PODXL may provide potential therapeutic targets for patients with radiotherapy-resistant CRC.
... The clinical significance of PODXL in the progression of various cancers has been studied, and it was found as a stem cell marker in the testicular cancer at the first time [3]. The later findings proved that, PODXL associates with advanced tumor phenotype in some cancers, including breast cancer [1,13], colorectal cancer [5,[14][15][16], esophageal cancer [17], gastric cancer [17][18][19], glioblastoma multiforme [20], lung adenocarcinoma [21], oral squamous cell carcinoma [4,22], ovarian cancer [23], pancreatic cancer [24][25][26][27], prostate cancer [28,29], renal cell carcinoma [30], urothelial bladder cancer [31], and so on. ...
Absract:
BACKGROUND: Several studies have investigated the associations between the podocalyxin-like protein (PODXL) expression quantity or locations and cancers survival, but the results were far from conclusive. Therefore, we proceeded a meta-analysis on PODXL in various human cancers to find its prognostic value and followed confirmation using the TCGA datasets.
Methods:
We performed a systematic search, and 18 citations, including 5705 patients were pooled in meta-analysis. The results were verified with TCGA datasets.
Results:
Total eligible studies comprised 5705 patients with 10 types of cancer. And the result indicated that PODXL high-expression or membrane-expression were significantly related to poor overall survival (OS). However, subgroup analysis showed a significant association between high expressed PODXL and poor OS in the colorectal cancer, pancreatic cancer, urothelial bladder cancer, renal cell carcinoma and glioblastoma multiforme. Then, we validated the inference using TCGA datasets, and the consistent results were demonstrated in patients with pancreatic cancer, glioblastoma multiforme, gastric cancer, esophageal cancer and lung adenocarcinoma.
Conclusion:
The result of meta-analysis showed that high expressed PODXL was significantly linked with poor OS in pancreatic cancer and glioblastoma multiforme, but not in gastric cancer, esophageal cancer or lung adenocarcinoma. And the membrane expression of PODXL might also associate with poor OS. PODXL may act as tumor promotor and may serve as a potential target for antitumor therapy.
... The clinical significance of PODXL in the progression of various cancers has been studied, and it was found as a stem cell marker in the testicular cancer at the first time [3]. The later findings proved that, PODXL associates with advanced tumor phenotype in some cancers, including breast cancer [13,1], colorectal cancer [5,[14][15][16], esophageal cancer [17], gastric cancer [18,19,17], glioblastoma multiforme [20], lung adenocarcinoma [21], oral squamous cell carcinoma [4,22], ovarian cancer [23], pancreatic cancer [24][25][26][27], prostate cancer [28,29], renal cell carcinoma [30], urothelial bladder cancer [31], and so on. We performed a meta-analysis at pooling data, in order to estimate the potential prognostic value of PODXL. ...
Background Several studies have investigated the associations between the podocalyxin-like protein (PODXL) expression quantity or locations and cancers survival, but the results were far from conclusive. Therefore, we proceeded a meta-analysis on PODXL in various human cancers to find its prognostic value and followed confirmation using the TCGA datasets.
Methods We performed a systematic search, and 18 citations, including 5705 patients were pooled in meta-analysis. The results were verified with TCGA datasets.
Results Total eligible studies comprised 5705 patients with 10 types of cancer. And the result indicated that PODXL high-expression or membrane-expression were significantly related to poor overall survival (OS). However, subgroup analysis showed a significant association between high expressed PODXL and poor OS in the colorectal cancer, pancreatic cancer, urothelial bladder cancer, renal cell carcinoma and glioblastoma multiforme. Then, we validated the inference using TCGA datasets, and the consistent results were demonstrated in patients with pancreatic cancer, glioblastoma multiforme, gastric cancer, esophageal cancer and lung adenocarcinoma.
Conclusion The result of meta-analysis showed that high expressed PODXL was significantly linked with poor OS in pancreatic cancer and glioblastoma multiforme, but not in gastric cancer, esophageal cancer or lung adenocarcinoma. And the membrane expression of PODXL might also associate with poor OS. PODXL may act as tumor promotor and may serve as a potential target for antitumor therapy.
... In SAS human oral squamous cell carcinoma cell line, silencing of PODXL abrogated cell proliferation and colony formation [46]. This effect was corroborated in vivo by transplanting PODXL-silenced HSC-2 oral squamous cell carcinoma cell line into nude mice, which resulted in both tumor volume and tumor weight reduction compared to that derived from parental HSC-2 cells [79]. ...
Mature B-cell non-Hodgkin lymphoma (B-NHL) constitutes a group of heterogeneous malignant lymphoproliferative diseases ranging from indolent to highly aggressive forms. Although the survival after chemo-immunotherapy treatment of mature B-NHL has increased over the last years, many patients relapse or remain refractory due to drug resistance, presenting an unfavorable prognosis. Hence, there is an urgent need to identify new prognostic markers and therapeutic targets. Podocalyxin (PODXL), a sialomucin overexpressed in a variety of tumor cell types and associated with their aggressiveness, has been implicated in multiple aspects of cancer progression, although its participation in hematological malignancies remains unexplored. New evidence points to a role for PODXL in mature B-NHL cell proliferation, survival, migration, drug resistance, and metabolic reprogramming, as well as enhanced levels of PODXL in mature B-NHL. Here, we review the current knowledge on the contribution of PODXL to tumorigenesis, highlighting and discussing its role in mature B-NHL progression.
PODXL, a protein that is dysregulated in multiple cancers, plays an important role in promoting cancer metastasis. In this study, we report that RNA editing promotes the inclusion of a PODXL alternative exon. The resulting edited PODXL long isoform is more prone to protease digestion and has the strongest effects on reducing cell migration and cisplatin chemoresistance among the three PODXL isoforms (short, unedited long, and edited long isoforms). Importantly, the editing level of the PODXL recoding site and the inclusion level of the PODXL alternative exon are strongly associated with overall patient survival in Kidney Renal Clear Cell Carcinoma (KIRC). Supported by a significant enrichment of exonic RNA editing sites in alternatively spliced exons, we hypothesize that exonic RNA editing sites may enhance proteomic diversity through alternative splicing, in addition to amino acid changes, a previously under-appreciated aspect of RNA editing function.
