CD44 splice variant (CD44v3) promotes progression of urothelial carcinoma of bladder through Akt/ERK/STAT3 pathways: novel therapeutic approach

Anand, Vivek; Khandelwal, Madhuram; Appunni, Sandeep; Gupta, Nidhi; Seth, Amlesh; Singh, Prabhjot; Mathur, Sandeep; Sharma, Alpana

doi:10.1007/s00432-019-03024-9

Cited by 31 publications

(26 citation statements)

References 38 publications

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“…In fact, it has been shown that in many types of solid tumors, increased synthesis of HA by cancer cells or by tumor stromal cells is correlated with tumor growth and metastasis [ 9 , 142 ]. Recent studies have confirmed that the over-expression of HAS2 promotes tumor progression in breast, ovarian, bladder, colorectal, pancreatic and lung carcinoma and resistance to chemotherapy [ 143 , 144 , 145 , 146 , 147 , 148 ]. On the other hand, it was proved that inhibiting HA synthesis inhibits also metastasis of carcinoma cells in some types of tumors [ 144 , 149 ].…”

Section: Medical Applications Of Ha and Its Derivativesmentioning

confidence: 99%

Hyaluronic Acid: Redefining Its Role

Abatangelo

Vindigni

Avruscio

et al. 2020

Cells

237

127

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The discovery of several unexpected complex biological roles of hyaluronic acid (HA) has promoted new research impetus for biologists and, the clinical interest in several fields of medicine, such as ophthalmology, articular pathologies, cutaneous repair, skin remodeling, vascular prosthesis, adipose tissue engineering, nerve reconstruction and cancer therapy. In addition, the great potential of HA in medicine has stimulated the interest of pharmaceutical companies which, by means of new technologies can produce HA and several new derivatives in order to increase both the residence time in a variety of human tissues and the anti-inflammatory properties. Minor chemical modifications of the molecule, such as the esterification with benzyl alcohol (Hyaff-11® biomaterials), have made possible the production of water-insoluble polymers that have been manufactured in various forms: membranes, gauzes, nonwoven meshes, gels, tubes. All these biomaterials are used as wound-covering, anti-adhesive devices and as scaffolds for tissue engineering, such as epidermis, dermis, micro-vascularized skin, cartilage and bone. In this review, the essential biological functions of HA and the applications of its derivatives for pharmaceutical and tissue regeneration purposes are reviewed.

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Section: Medical Applications Of Ha and Its Derivativesmentioning

confidence: 99%

Hyaluronic Acid: Redefining Its Role

Abatangelo

Vindigni

Avruscio

et al. 2020

Cells

237

127

View full text Add to dashboard Cite

show abstract

“…In agreement with these observations, monoclonal antibodies targeting the CD44s isoform reduce CSC percentage in cultured pancreatic cancer cells and in xenograft mouse models, along with downregulating STAT3 levels and STAT3-mediated target gene expression ( 79 ). In breast and urinary bladder cancer cell lines, CD44 knockdown inhibits cell invasion and tumorigenicity via STAT3 phosphorylation blockade, while anti-CD44 blocking antibody treatment downregulates STAT3 levels in rat atrial fibroblasts, suggesting that CD44 can regulate both STAT3 expression and activation ( 80 – 83 ). In turn, well known STAT3 activators IL-6 ( 84 ) and IGF-1 ( 85 ) have been shown to significantly induce CD44 promoter activity in pancreatic tumor cells ( 12 ), while in hepatocytes several putative STAT3 binding sites have been described within the CD44 promoter, demonstrating that STAT3 can directly induce CD44 expression ( 86 ).…”

Section: Cd44 and Stat3 Crosstalk In Cancermentioning

confidence: 99%

CD44 in Ovarian Cancer Progression and Therapy Resistance—A Critical Role for STAT3

Martincuks

Zhao

et al. 2020

Front. Oncol.

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Despite significant progress in cancer therapy over the last decades, ovarian cancer remains the most lethal gynecologic malignancy worldwide with the five-year overall survival rate less than 30% due to frequent disease recurrence and chemoresistance. CD44 is a non-kinase transmembrane receptor that has been linked to cancer metastatic progression, cancer stem cell maintenance, and chemoresistance development via multiple mechanisms across many cancers, including ovarian, and represents a promising therapeutic target for ovarian cancer treatment. Moreover, CD44-mediated signaling interacts with other well-known pro-tumorigenic pathways and oncogenes during cancer development, such as signal transducer and activator of transcription 3 (STAT3). Given that both CD44 and STAT3 are strongly implicated in the metastatic progression and chemoresistance of ovarian tumors, this review summarizes currently available evidence about functional crosstalk between CD44 and STAT3 in human malignancies with an emphasis on ovarian cancer. In addition to the role of tumor cell-intrinsic CD44 and STAT3 interaction in driving cancer progression and metastasis, we discuss how CD44 and STAT3 support the pro-tumorigenic tumor microenvironment and promote tumor angiogenesis, immunosuppression, and cancer metabolic reprogramming in favor of cancer progression. Finally, we review the current state of therapeutic CD44 targeting and propose superior treatment possibilities for ovarian cancer.

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“…On the other hand, molecular pathways, such as STAT3 participate in bladder cancer progression [ 219 ]. STAT3 can individually promote the proliferation of bladder cancer cells [ 220 ], or it may be targeted by upstream mediators, such as Akt/ERK [ 221 ]. Administration of chrysin is correlated with an increase in ROS levels to down-regulate STAT3 expression.…”

Section: Chrysin and Cancermentioning

confidence: 99%

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

et al. 2020

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Pharmacological profile of phytochemicals has attracted much attention to their use in disease therapy. Since cancer is a major problem for public health with high mortality and morbidity worldwide, experiments have focused on revealing the anti-tumor activity of natural products. Flavonoids comprise a large family of natural products with different categories. Chrysin is a hydroxylated flavonoid belonging to the flavone category. Chrysin has demonstrated great potential in treating different disorders, due to possessing biological and therapeutic activities, such as antioxidant, anti-inflammatory, hepatoprotective, neuroprotective, etc. Over recent years, the anti-tumor activity of chrysin has been investigated, and in the present review, we provide a mechanistic discussion of the inhibitory effect of chrysin on proliferation and invasion of different cancer cells. Molecular pathways, such as Notch1, microRNAs, signal transducer and activator of transcription 3 (STAT3), nuclear factor-kappaB (NF-κB), PI3K/Akt, MAPK, etc., as targets of chrysin are discussed. The efficiency of chrysin in promoting anti-tumor activity of chemotherapeutic agents and suppressing drug resistance is described. Moreover, poor bioavailability, as one of the drawbacks of chrysin, is improved using various nanocarriers, such as micelles, polymeric nanoparticles, etc. This updated review will provide a direction for further studies in evaluating the anti-tumor activity of chrysin.

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CD44 splice variant (CD44v3) promotes progression of urothelial carcinoma of bladder through Akt/ERK/STAT3 pathways: novel therapeutic approach

Cited by 31 publications

References 38 publications

Hyaluronic Acid: Redefining Its Role

Hyaluronic Acid: Redefining Its Role

CD44 in Ovarian Cancer Progression and Therapy Resistance—A Critical Role for STAT3

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

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