Claudin-2 inhibits renal clear cell carcinoma progression by inhibiting YAP-activation

Kumar, Balawant; Ahmad, Rizwan; Giannico, Giovanna A.; Zent, Roy; Talmon, Geoffrey A.; Harris, Raymond C.; Clark, Peter E.; Lokeshwar, Vinata B.; Dhawan, Punita; Singh, Amar B.

doi:10.1186/s13046-021-01870-5

Cited by 21 publications

(16 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CLDN18 interacts with p–YAP to inhibit YAP nuclear localization in progenitors of distal lung epithelium AT2 cells [ 40 ]. Dependent on the PBM, CLDN2 binds to and regulates the nuclear expression and activation of YAP [ 41 ]. The nuclear expression and activity of TAZ are also regulated by the upstream kinases of the Hippo pathway and other kinases such as c–SRC [ 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

CLDN6 Suppresses c–MYC–Mediated Aerobic Glycolysis to Inhibit Proliferation by TAZ in Breast Cancer

Wang

et al. 2021

IJMS

View full text Add to dashboard Cite

Claudin 6 (CLDN6) was found to be a breast cancer suppressor gene, which is lowly expressed in breast cancer and inhibits breast cancer cell proliferation upon overexpression. However, the mechanism by which CLDN6 inhibits breast cancer proliferation is unclear. Here, we investigated this issue and elucidated the molecular mechanisms by which CLDN6 inhibits breast cancer proliferation. First, we verified that CLDN6 was lowly expressed in breast cancer tissues and that patients with lower CLDN6 expression had a worse prognosis. Next, we confirmed that CLDN6 inhibited breast cancer proliferation through in vitro and in vivo experiments. As for the mechanism, we found that CLDN6 inhibited c–MYC–mediated aerobic glycolysis based on a metabolomic analysis of CLDN6 affecting cellular lactate levels. CLDN6 interacted with a transcriptional co–activator with PDZ-binding motif (TAZ) and reduced the level of TAZ, thereby suppressing c–MYC transcription, which led to a reduction in glucose uptake and lactate production. Considered together, our results suggested that CLDN6 suppressed c–MYC–mediated aerobic glycolysis to inhibit the proliferation of breast cancer by TAZ, which indicated that CLDN6 acted as a novel regulator of aerobic glycolysis and provided a theoretical basis for CLDN6 as a biomarker of progression in breast cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

CLDN6 Suppresses c–MYC–Mediated Aerobic Glycolysis to Inhibit Proliferation by TAZ in Breast Cancer

Wang

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Although experimental and clinical studies have explored the function of CLDN2 in various cancer initiation and development processes, 23 , 24 , 25 , 26 the precise role and underlying mechanism of CLDN2 in CRC remain largely unclear. Our study provides evidence illustrating that CLDN2 promotes colorectal cancer progression by suppressing NDRG1 expression via stabilising CLDN2/ZO1/ZONAB complex.…”

Section: Discussionmentioning

confidence: 99%

Claudin‐2 promotes colorectal cancer growth and metastasis by suppressing NDRG1 transcription

Wei

Zhang

Yang

et al. 2021

Clinical & Translational Med

View full text Add to dashboard Cite

Colorectal cancer (CRC) is one of the most common malignant tumours, with multiple driving factors and biological transitions involved in its development. Claudin‐2 (CLDN2), a well‐defined component of cellular tight junction, has been indicated to associate with CRC progression. However, the function of CLDN2 and the underlying mechanism whereby the downstream signalling transduction is regulated in CRC remains largely unclear. In this study, we demonstrated that CLDN2 is upregulated in CRC samples and associated with poor survival. And CLDN2 depletion significantly promotes N‐myc downstream‐regulated gene 1 (NDRG1) transcription, leading to termination of the CRC growth and metastasis in vitro and in vivo. Mechanistically, this process promotes CLDN2/ZO1/ZONAB complex dissociation and ZONAB shuttle into nucleus to enrich in the promoter of NDRG1. Thus, this study reveals a novel CLDN2/ZO1/ZONAB‐NDRG1 axis in CRC by regulating the expression of EMT‐related genes and CDKIs, suggesting CLDN2 may serve as a promising target for CRC treatment.

show abstract

“…TGF-β signaling or hypoxia plays an important role in the regulation of renal clear cell carcinoma. For example, loss of claudin-2 regulates the Hippo signaling and nuclear localization of YAP and induces EMT 14 .…”

Section: Introductionmentioning

confidence: 99%

Renal cell carcinoma-derived exosomes deliver lncARSR to induce macrophage polarization and promote tumor progression via STAT3 pathway

Zhang

Zheng

et al. 2022

Int. J. Biol. Sci.

View full text Add to dashboard Cite

Tumor-derived exosomes play a pivotal role in regulating tumor progression by mediating crosstalk between tumor cells and immune cells such as macrophages within the tumor microenvironment. Macrophages can adopt two distinct polarization statuses and switch between M1 or M2 activation phenotypes in response to the different external stimuli. However, the role of tumor derived exosomes in the macrophage phenotypic switch and tumor development have not been elucidated in renal cell carcinoma (RCC). Here we found that high macrophage infiltration was associated with worse prognosis in RCC patients, therefore we propose our hypothesis that RCC derived exosomes might directly influence macrophage polarization and thus promote tumor progression. Both cell-based in vitro models and orthotopic transplantation in vivo tumor models were constructed and ELISA, flow cytometry, and macrophage functional studies were performed to investigate whether and how RCC-derived exosomes regulate macrophage polarization and tumor growth. The results found that these exosomes promote macrophage polarization, cytokine release, phagocytosis, angiogenesis, and tumor development. Further study revealed high amount of a recently discovered lncRNA called lncARSR in RCC-derived exosomes. Overexpression of lncARSR induced phenotypic and functional changes of macrophages in vitro and promoted tumor growth in vivo , while knockdown of lncARSR by siRNA disrupted the exosomes-mediated macrophage polarization. LncARSR interacts directly with miR-34/miR- 449 to increase STAT3 expression and mediate macrophage polarization in RCC cells. Together, RCC-derived exosomes facilitate the development of tumor through inducing macrophage polarization via transferring lncARSR, suggesting that RCC-derived exosomes, lncARSR and STAT3 are the potential therapeutic targets for treatment of RCC.

show abstract

Claudin-2 inhibits renal clear cell carcinoma progression by inhibiting YAP-activation

Cited by 21 publications

References 52 publications

CLDN6 Suppresses c–MYC–Mediated Aerobic Glycolysis to Inhibit Proliferation by TAZ in Breast Cancer

CLDN6 Suppresses c–MYC–Mediated Aerobic Glycolysis to Inhibit Proliferation by TAZ in Breast Cancer

Claudin‐2 promotes colorectal cancer growth and metastasis by suppressing NDRG1 transcription

Renal cell carcinoma-derived exosomes deliver lncARSR to induce macrophage polarization and promote tumor progression via STAT3 pathway

Contact Info

Product

Resources

About