ΔNp63α promotes adhesion of metastatic prostate cancer cells to the bone through regulation of CD82

Giacomo, Viviana di; Tian, Tian V.; Mas, Amandine; Pecoraro, Matteo; Batlle-Morera, Laura; Noya, L; Juan, Manel; Ruberte, Jesús; Keyes, William M.

doi:10.1038/onc.2017.42

Cited by 17 publications

(11 citation statements)

References 48 publications

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“… 23 , 24 PC3 is a bone metastatic PCa cell line, which promotes high osteolytic lesions with minimal or no osteoblastic function. 25 , 26 Osteoclast precursors were isolated from the bone marrow of C57BL6 mice (forelimbs and hind limbs) and were differentiated using RANKL and M-CSF (control condition) and conditioned medium (CM) from PC3 and LNCaP C4-2B cells separately. M-CSF and RANKL signaling is central to osteoclast differentiation under physiological condition.…”

Section: Resultsmentioning

confidence: 99%

Tumor- and osteoclast-derived NRP2 in prostate cancer bone metastases

et al. 2021

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Understanding the role of neuropilin 2 (NRP2) in prostate cancer cells as well as in the bone microenvironment is pivotal in the development of an effective targeted therapy for the treatment of prostate cancer bone metastasis. We observed a significant upregulation of NRP2 in prostate cancer cells metastasized to bone. Here, we report that targeting NRP2 in cancer cells can enhance taxane-based chemotherapy with a better therapeutic outcome in bone metastasis, implicating NRP2 as a promising therapeutic target. Since, osteoclasts present in the tumor microenvironment express NRP2, we have investigated the potential effect of targeting NRP2 in osteoclasts. Our results revealed NRP2 negatively regulates osteoclast differentiation and function in the presence of prostate cancer cells that promotes mixed bone lesions. Our study further delineated the molecular mechanisms by which NRP2 regulates osteoclast function. Interestingly, depletion of NRP2 in osteoclasts in vivo showed a decrease in the overall prostate tumor burden in the bone. These results therefore indicate that targeting NRP2 in prostate cancer cells as well as in the osteoclastic compartment can be beneficial in the treatment of prostate cancer bone metastasis.

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Section: Resultsmentioning

confidence: 99%

Tumor- and osteoclast-derived NRP2 in prostate cancer bone metastases

et al. 2021

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“…The other isoform is the ΔN isoform, which is predominantly expressed in the basal epithelial layer of mammary glands, skin, esophagus, and prostate [4][5][6][7][8], and plays key roles in tissue homeostasis. Additionally, ΔNp63 can have oncogenic functions in a number of cancers including breast, prostate, and head squamous cell carcinoma [4,[9][10][11]. In our earlier study, we found that ΔNp63 is critically involved in maintaining the stem-like/basal state of the mammary epithelium in normal development and basal breast cancer via activation of Wnt signaling [4].…”

Section: Abstract: δNp63; Mammary Gland; Oxphos; Polarity; Stem Cellsmentioning

confidence: 94%

Inducible knockout of ∆Np63 alters cell polarity and metabolism during pubertal mammary gland development

et al. 2019

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The ∆Np63 isoform of the p53‐family transcription factor Trp63 is a key regulator of mammary epithelial stem cells that is involved in breast cancer development. To investigate the role of ∆Np63 at different stages of normal mammary gland development, we generated a ∆Np63‐inducible conditional knockout (cKO) mouse model. We demonstrate that the deletion of ∆Np63 at puberty results in depletion of mammary stem cell‐enriched basal cells, reduces expression of E‐cadherin and β‐catenin, and leads to a closed ductal lumen. RNA‐sequencing analysis reveals reduced expression of oxidative phosphorylation (OXPHOS)‐associated proteins and desmosomal polarity proteins. Functional assays show reduced numbers of mitochondria in the mammary epithelial cells of ΔNp63 cKO compared to wild‐type, supporting the reduced OXPHOS phenotype. These findings identify a novel role for ∆Np63 in cellular metabolism and mammary epithelial cell polarity.

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“…Sustained expression of ∆Np63α tends to promote the well-differentiated SCC phenotype and restricts epithelial–mesenchymal transition induced by TGF-β [ 42 ]. However, both suppressive [ 43 – 45 ] and promotive roles [ 46 ] of ∆Np63α in cell invasion and metastasis have been demonstrated in various cell contexts, suggesting a cell context-specific role in cancer metastasis. Growing evidence demonstrates that ΔNp63 exerts both a suppressive and promotive role on target genes expression [ 47 – 49 ].…”

Section: Introductionmentioning

confidence: 99%

TP63 links chromatin remodeling and enhancer reprogramming to epidermal differentiation and squamous cell carcinoma development

Man

Tan

Wang

et al. 2020

Cell. Mol. Life Sci.

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Squamous cell carcinoma (SCC) is an aggressive malignancy that can originate from various organs. TP63 is a master regulator that plays an essential role in epidermal differentiation. It is also a lineage-dependent oncogene in SCC. ΔNp63α is the prominent isoform of TP63 expressed in epidermal cells and SCC, and overexpression promotes SCC development through a variety of mechanisms. Recently, ΔNp63α was highlighted to act as an epidermal-specific pioneer factor that binds closed chromatin and enhances chromatin accessibility at epidermal enhancers. ΔNp63α coordinates chromatin-remodeling enzymes to orchestrate the tissue-specific enhancer landscape and three-dimensional high-order architecture of chromatin. Moreover, ΔNp63α establishes squamous-like enhancer landscapes to drive oncogenic target expression during SCC development. Importantly, ΔNp63α acts as an upstream regulator of super enhancers to activate a number of oncogenic transcripts linked to poor prognosis in SCC. Mechanistically, ΔNp63α activates genes transcription through physically interacting with a number of epigenetic modulators to establish enhancers and enhance chromatin accessibility. In contrast, ΔNp63α also represses gene transcription via interacting with repressive epigenetic regulators. ΔNp63α expression is regulated at multiple levels, including transcriptional, post-transcriptional, and post-translational levels. In this review, we summarize recent advances of p63 in epigenomic and transcriptional control, as well as the mechanistic regulation of p63.

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ΔNp63α promotes adhesion of metastatic prostate cancer cells to the bone through regulation of CD82

Cited by 17 publications

References 48 publications

Tumor- and osteoclast-derived NRP2 in prostate cancer bone metastases

Tumor- and osteoclast-derived NRP2 in prostate cancer bone metastases

Inducible knockout of ∆Np63 alters cell polarity and metabolism during pubertal mammary gland development

TP63 links chromatin remodeling and enhancer reprogramming to epidermal differentiation and squamous cell carcinoma development

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