The human cancer and stem cell marker podocalyxin interacts with the glucose-3-transporter in malignant pluripotent stem cells

Schopperle, William M.; Lee, Jung M.; DeWolf, William C.

doi:10.1016/j.bbrc.2010.06.074

Cited by 14 publications

(10 citation statements)

References 38 publications

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“…This requirement for podocalyxin seemed to be related to responses to TGF-β as the basal levels of vimentin and E-cadherin were comparable in untreated control and PODOXL-KD cells. These coordinated regulations are consistent with a recent report indicating that in pluripotent stem cells podocalyxin interacted with the glucose-3-transporter and the levels of both molecules were coordinately regulated [41]. Collectively these results suggest that podocalyxin is an important component of a regulatory network in TGF-β induced EMT like behavior.…”

Section: Discussionsupporting

confidence: 92%

Requirement of Podocalyxin in TGF-Beta Induced Epithelial Mesenchymal Transition

2011

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Epithelial mesenchymal transition (EMT) is characterized by the development of mesenchymal properties such as a fibroblast-like morphology with altered cytoskeletal organization and enhanced migratory potential. We report that the expression of podocalyxin (PODXL), a member of the CD34 family, is markedly increased during TGF-β induced EMT. PODXL is enriched on the leading edges of migrating A549 cells. Silencing of podocalyxin expression reduced cell ruffle formation, spreading, migration and affected the expression patterns of several proteins that normally change during EMT (e.g., vimentin, E-cadherin). Cytoskeletion assembly in EMT was also found to be dependent on the production of podocalyin. Compositional analysis of podocalyxin containing immunoprecipitates revealed that collagen type 1 was consistently associated with these isolates. Collagen type 1 was also found to co-localize with podocalyxin on the leading edges of migrating cells. The interactions with collagen may be a critical aspect of podocalyxin function. Podocalyxin is an important regulator of the EMT like process as it regulates the loss of epithelial features and the acquisition of a motile phenotype.

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Section: Discussionsupporting

confidence: 92%

Requirement of Podocalyxin in TGF-Beta Induced Epithelial Mesenchymal Transition

2011

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“…The participation of PODXL in cell metabolism remains unexplored. PODXL has been reported to upregulate and form a complex with the glucose-transporter 3 (GLUT3) in embryonal carcinoma cancer stem cells [134]. On the other hand, glucose has been found to modulate PODXL expression in both normal and malignant cells [27,135,136].…”

Section: Podxl In Cancer Cell Metabolismmentioning

confidence: 99%

Emerging Role of Podocalyxin in the Progression of Mature B-Cell Non-Hodgkin Lymphoma

Tamayo-Orbegozo

Amo

Díez-García

et al. 2020

Cancers

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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.

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“…TRA-1-60 is a carbohydrate epitope of the cell surface sialylated keratan sulfate proteoglycan podocalyxin [18] , [47] found in human stem cells [18] , cancer stem cells [48] and embryonal cancers [49] . Podocalyxin prevents cell adhesion and promotes metastasis.…”

Section: Discussionmentioning

confidence: 99%

Increased Cycling Cell Numbers and Stem Cell Associated Proteins as Potential Biomarkers for High Grade Human Papillomavirus+ve Pre-Neoplastic Cervical Disease

et al. 2014

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High risk (oncogenic) human papillomavirus (HPV) infection causes cervical cancer. Infections are common but most clear naturally. Persistent infection can progress to cancer. Pre-neoplastic disease (cervical intraepithelial neoplasia/CIN) is classified by histology (CIN1-3) according to severity. Cervical abnormalities are screened for by cytology and/or detection of high risk HPV but both methods are imperfect for prediction of which women need treatment. There is a need to understand the host virus interactions that lead to different disease outcomes and to develop biomarker tests for accurate triage of infected women. As cancer is increasingly presumed to develop from proliferative, tumour initiating, cancer stem cells (CSCs), and as other oncogenic viruses induce stem cell associated gene expression, we evaluated whether presence of mRNA (detected by qRT-PCR) or proteins (detected by flow cytometry and antibody based proteomic microarray) from stem cell associated genes and/or increased cell proliferation (detected by flow cytometry) could be detected in well-characterised, routinely collected cervical samples from high risk HPV+ve women. Both cytology and histology results were available for most samples with moderate to high grade abnormality. We found that stem cell associated proteins including human chorionic gonadotropin, the oncogene TP63 and the transcription factor SOX2 were upregulated in samples from women with CIN3 and that the stem cell related, cell surface, protein podocalyxin was detectable on cells in samples from a subset of women with CIN3. SOX2, TP63 and human gonadotrophin mRNAs were upregulated in high grade disease. Immunohistochemistry showed that SOX2 and TP63 proteins clearly delineated tumour cells in invasive squamous cervical cancer. Samples from women with CIN3 showed increased proliferating cells. We believe that these markers may be of use to develop triage tests for women with high grade cervical abnormality to distinguish those who may progress to cancer from those who may be treated more conservatively.

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The human cancer and stem cell marker podocalyxin interacts with the glucose-3-transporter in malignant pluripotent stem cells

Cited by 14 publications

References 38 publications

Requirement of Podocalyxin in TGF-Beta Induced Epithelial Mesenchymal Transition

Requirement of Podocalyxin in TGF-Beta Induced Epithelial Mesenchymal Transition

Emerging Role of Podocalyxin in the Progression of Mature B-Cell Non-Hodgkin Lymphoma

Increased Cycling Cell Numbers and Stem Cell Associated Proteins as Potential Biomarkers for High Grade Human Papillomavirus+ve Pre-Neoplastic Cervical Disease

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