The expression of S100A8/S100A9 is inducible and regulated by the Hippo/YAP pathway in squamous cell carcinomas

Li, Yunguang; Kong, Fei; Chang, Jin; Hu, Enze; Shao, Qirui; Liu, Jin; He, Dacheng; Xiao, Xueyuan

doi:10.1186/s12885-019-5784-0

Cited by 12 publications

(10 citation statements)

References 53 publications

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“…Similar to our finding, lamellipodium-related gastric cancer migration is also governed by Yap through the SIRT1-Mfn2 pathway [67]. In squamous cell carcinomas [68] and endometrial cancer [69], F-actin homeostasis is also sustained by Yap. erefore, our results provide a novel insight into the molecular mechanism underlying breast cancer migration.…”

Section: Discussionsupporting

confidence: 90%

Yap-Hippo Signaling Activates Mitochondrial Protection and Sustains Breast Cancer Viability under Hypoxic Stress

Chen

Zhang

Guo

et al. 2021

Journal of Oncology

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Yes-associated protein (Yap) is a transcriptional regulator that upregulates oncogenes and downregulates tumor repressor genes. In this study, we analyzed protein expression, RNA transcription, and signaling pathways to determine the function and mechanism of Yap in breast cancer survival during hypoxic stress. Yap transcription was drastically upregulated by hypoxia in a time-dependent manner. siRNA-mediated Yap knockdown attenuated breast cancer viability and impaired cell proliferation under hypoxic conditions. Yap knockdown induced mitochondrial stress, including mitochondrial membrane potential reduction, mitochondrial oxidative stress, and ATP exhaustion after exposure to hypoxia. It also repressed mitochondrial protective systems, including mitophagy and mitochondrial fusion upon exposure to hypoxia. Finally, our data showed that Yap knockdown suppresses MCF-7 cell migration by inhibiting F-actin transcription and promoting lamellipodium degradation under hypoxic stress. Taken together, Yap maintenance of mitochondrial function and activation of F-actin/lamellipodium signaling is required for breast cancer survival, migration, and proliferation under hypoxic stress.

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Section: Discussionsupporting

confidence: 90%

Yap-Hippo Signaling Activates Mitochondrial Protection and Sustains Breast Cancer Viability under Hypoxic Stress

Chen

Zhang

Guo

et al. 2021

Journal of Oncology

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“…S100A8 is a nuclear factor-κB target gene but needs the synergistic function of other transcriptional regulators [35]. Although YAP did not bind on S100A8 promoter sites, the activated Hippo pathway upregulated S100A8 expression in squamous cell carcinoma [36]. The ubiquitin ligase RNF5 interacted with S100A8 and promoted its degradation [37].…”

Section: Discussionmentioning

confidence: 99%

S100A8 promotes epithelial‐mesenchymal transition and metastasis under TGF‐β/USF2 axis in colorectal cancer

Zhang

Qian

et al. 2021

Cancer Communications

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Background: The transforming growth factor-β (TGF-β) pathway plays a pivotal role in inducing epithelial-mesenchymal transition (EMT), which is a key step in cancer invasion and metastasis. However, the regulatory mechanism of TGFβ in inducing EMT in colorectal cancer (CRC) has not been fully elucidated. In previous studies, it was found that S100A8 may regulate EMT. This study aimed to clarify the role of S100A8 in TGF-β-induced EMT and explore the underlying mechanism in CRC. Methods: S100A8 and upstream transcription factor 2 (USF2) expression was detected by immunohistochemistry in 412 CRC tissues. Kaplan-Meier survival analysis was performed. In vitro, Western blot, and migration and invasion assays were performed to investigate the effects of S100A8 and USF2 on TGF-β-induced EMT. Mouse metastasis models were used to determine in vivo metastasis ability. Luciferase reporter and chromatin immunoprecipitation assay were used to explore the role of USF2 on S100A8 transcription. Results: During TGF-β-induced EMT in CRC cells, S100A8 and the transcription factor USF2 were upregulated. S100A8 promoted cell migration and invasion and EMT. USF2 transcriptionally regulated S100A8 expression by directly binding to its promoter region. Furthermore, TGF-β enhanced the USF2/S100A8 signaling axis of CRC cells whereas extracellular S100A8 inhibited the USF2/S100A8 axis of CRC cells. S100A8 expression in tumor cells was associated with poor overall survival in CRC. USF2 expression was positively related to S100A8 expression in tumor cells but negatively related to S100A8-positive stromal cells.

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“…Several soluble factors and cells have been identified in the pre-metastatic niche formation, such as growth factors secreted by tumor cells, bone marrow-derived cells (BMDCs), extracellular vesicles (EVs), suppressive immune cells and host tissue stromal cells [18]. In more detail, the primary tumor cells were found to secrete pro-inflammatory factors such as vascular endothelial growth factor A (VEGF-A), transforming growth factor β (TGFβ) and tumor necrosis factor α (TNFα) that, in turn, induce the expression of chemoattractants such as S100A8 and S100A9 (a calcium-binding protein family) [19,20,21]. The increased expression of S100A8/S100A9 promotes cell proliferation and inhibits cell differentiation and apoptosis, thus contributing to the onset of a metastasis favorable environment.…”

Section: Premetastatic Niche and Tumor Microenvironmentmentioning

confidence: 99%

Extracellular Matrix Alterations in Metastatic Processes

Paolillo

Schinelli

2019

IJMS

262

191

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The extracellular matrix (ECM) is a complex network of extracellular-secreted macromolecules, such as collagen, enzymes and glycoproteins, whose main functions deal with structural scaffolding and biochemical support of cells and tissues. ECM homeostasis is essential for organ development and functioning under physiological conditions, while its sustained modification or dysregulation can result in pathological conditions. During cancer progression, epithelial tumor cells may undergo epithelial-to-mesenchymal transition (EMT), a morphological and functional remodeling, that deeply alters tumor cell features, leading to loss of epithelial markers (i.e., E-cadherin), changes in cell polarity and intercellular junctions and increase of mesenchymal markers (i.e., N-cadherin, fibronectin and vimentin). This process enhances cancer cell detachment from the original tumor mass and invasiveness, which are necessary for metastasis onset, thus allowing cancer cells to enter the bloodstream or lymphatic flow and colonize distant sites. The mechanisms that lead to development of metastases in specific sites are still largely obscure but modifications occurring in target tissue ECM are being intensively studied. Matrix metalloproteases and several adhesion receptors, among which integrins play a key role, are involved in metastasis-linked ECM modifications. In addition, cells involved in the metastatic niche formation, like cancer associated fibroblasts (CAF) and tumor associated macrophages (TAM), have been found to play crucial roles in ECM alterations aimed at promoting cancer cells adhesion and growth. In this review we focus on molecular mechanisms of ECM modifications occurring during cancer progression and metastatic dissemination to distant sites, with special attention to lung, liver and bone. Moreover, the functional role of cells forming the tumor niche will also be reviewed in light of the most recent findings.

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The expression of S100A8/S100A9 is inducible and regulated by the Hippo/YAP pathway in squamous cell carcinomas

Cited by 12 publications

References 53 publications

Yap-Hippo Signaling Activates Mitochondrial Protection and Sustains Breast Cancer Viability under Hypoxic Stress

Yap-Hippo Signaling Activates Mitochondrial Protection and Sustains Breast Cancer Viability under Hypoxic Stress

S100A8 promotes epithelial‐mesenchymal transition and metastasis under TGF‐β/USF2 axis in colorectal cancer

Extracellular Matrix Alterations in Metastatic Processes

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