BRAF-activated WT1 contributes to cancer growth and regulates autophagy and apoptosis in papillary thyroid carcinoma

Chen, Xing; Lin, Shan; Lin, Ying Q.; Wu, Songsong; Zhuo, Minling; Zhang, Ailong; Zheng, Junjie; You, Zhebin

doi:10.1186/s12967-022-03260-7

Cited by 11 publications

(4 citation statements)

References 48 publications

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“…6f). Among them, WT1 has recently been identified to up-regulates ERK/MAPK activity and cell proliferation ( 78 ), while ELK1 and STAT3 are direct downstream targets of ERK/MAPK that have been shown to control cell growth ( 79, 80 ). We then used IF to examine the proliferation marker Ki-67 ( 81 ), and quantify cell proliferation by calculating the fraction of Ki-67 active cells.…”

Section: Resultsmentioning

confidence: 99%

Cytoskeletal activation of NHE1 regulates mechanosensitive cell volume adaptation and proliferation

Ni,

Ge,

et al. 2023

Preprint

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The regulation of mammalian cell volume is crucial for maintaining key cellular processes. Cells can rapidly respond to osmotic and hydrostatic pressure imbalances during environmental challenges, generating fluxes of water and ions that alter volume within minutes. While the role of ion pump and leak in cell volume regulation has been well-established, the role of the actomyosin cytoskeleton and its substantial interplay with ion transporters are still unclear. In this work, we discover a system of cell volume regulation controlled by cytoskeletal activation of ion transporters. Under hypotonic shock, NIH-3T3 and MCF-10A display a 20% secondary volume increase (SVI) following the initial regulatory volume decrease. We show that SVI is initiated by Ca2+influx through stretch activated channel Piezo1 and subsequent actomyosin remodeling. Rather than contracting cells, actomyosin triggers cell swelling by activating Na+-H+exchanger 1 (NHE1) through their co-binding partner ezrin. Cytoskeletal activation of NHE1 can be similarly triggered by mechanical stretch and attenuated by soft substrates. This mechanism is absent in certain cancer cell lines such as HT1080 and MDA-MB-231, where volume regulation is dominated by intrinsic response of ion transporters. Moreover, cytoskeletal activation of NHE1 during SVI induces nuclear deformation, leading to DNA demethylation and a significant, immediate transcriptomic response in 3T3 cells, a phenomenon that is absent in HT1080 cells. Overall, our findings reveal the central role of Ca2+and actomyosin-mediated mechanosensation in the regulation of ion transport, cell volume, DNA methylation, and transcriptomics.

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Section: Resultsmentioning

confidence: 99%

Cytoskeletal activation of NHE1 regulates mechanosensitive cell volume adaptation and proliferation

Ni,

Ge,

et al. 2023

Preprint

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“…Since BRAF gene mutations, which are a component of the RAF/MEK/ERK pathway, are commonly found in melanoma and papillary thyroid cancer, few studies have investigated its presence in PA [ 33 , 152 , 153 , 154 ]. In 50 human pituitary adenomas, including 25 NFPA and 25 secreting adenomas (10 GH, 5 PRL, 6 LH and/or FSH, 4 GH/PRL), only one V600E mutation in a NFPA sample was found, suggesting that B-RAF mutations are a rare event in pituitary tumorigenesis [ 153 ].…”

Section: Discussionmentioning

confidence: 99%

The Role of Activation of PI3K/AKT/mTOR and RAF/MEK/ERK Pathways in Aggressive Pituitary Adenomas—New Potential Therapeutic Approach—A Systematic Review

Derwich

Sykutera

Bromińska

et al. 2023

IJMS

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Pituitary tumors (PT) are mostly benign, although occasionally they demonstrate aggressive behavior, invasion of surrounding tissues, rapid growth, resistance to conventional treatments, and multiple recurrences. The pathogenesis of PT is still not fully understood, and the factors responsible for its invasiveness, aggressiveness, and potential for metastasis are unknown. RAF/MEK/ERK and mTOR signaling are significant pathways in the regulation of cell growth, proliferation, and survival, its importance in tumorigenesis has been highlighted. The aim of our review is to determine the role of the activation of PI3K/AKT/mTOR and RAF/MEK/ERK pathways in the pathogenesis of pituitary tumors. Additionally, we evaluate their potential in a new therapeutic approach to provide alternative therapies and improved outcomes for patients with aggressive pituitary tumors that do not respond to standard treatment. We perform a systematic literature search using the PubMed, Embase, and Scopus databases (search date was 2012–2023). Out of the 529 screened studies, 13 met the inclusion criteria, 7 related to the PI3K/AKT/mTOR pathway, and 7 to the RAF/MEK/ERK pathway (one study was used in both analyses). Understanding the specific factors involved in PT tumorigenesis provides opportunities for targeted therapies. We also review the possible new targeted therapies and the use of mTOR inhibitors and TKI in PT management. Although the RAF/MEK/ERK and PI3K/AKT/mTOR pathways play a pivotal role in the complex signaling network along with many interactions, further research is urgently needed to clarify the exact functions and the underlying mechanisms of these signaling pathways in the pathogenesis of pituitary adenomas and their role in its invasiveness and aggressive clinical outcome.

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“…Autophagy inhibition by sonic hedgehog (Shh)-associated TGF-β-activated kinase (TAK1) siRNA has been demonstrated to potentiate GANT61 (a Shh pathway inhibitor)-induced apoptotic and antiproliferative effects, reflecting a cytoprotective role of autophagy in SW1736 ATC cells [ 66 ]. Autophagy suppression and apoptosis promotion are also observed in Wilms’ tumor 1 (WT1)-knockdown IHH4 and BCPAP cells [ 67 ]. Conversely, ASAP1 (ArfGAP with SH3 Domain, Ankyrin Repeat and PH Domain1) knockdown in PTC MDA-T32 and MDA-T85 cells triggers formation of autophagosomes and promotes autophagy through the mTOR pathway.…”

Section: Autophagy Participates In Tc Progressionmentioning

confidence: 99%

The new insights into autophagy in thyroid cancer progression

2023

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In recent decades, the incidence of thyroid cancer keeps growing at a shocking rate, which has aroused increasing concerns worldwide. Autophagy is a fundamental and ubiquitous biological event conserved in mammals including humans. Basically, autophagy is a catabolic process that cellular components including small molecules and damaged organelles are degraded for recycle to meet the energy needs, especially under the extreme conditions. The dysregulated autophagy has indicated to be involved in thyroid cancer progression. The enhancement of autophagy can lead to autophagic cell death during the degradation while the produced energies can be utilized by the rest of the cancerous tissue, thus this influence could be bidirectional, which plays either a tumor-suppressive or oncogenic role. Accordingly, autophagy can be suppressed by therapeutic agents and is thus regarded as a drug target for thyroid cancer treatments. In the present review, a brief description of autophagy and roles of autophagy in tumor context are given. We have addressed summary of the mechanisms and functions of autophagy in thyroid cancer. Some potential autophagy-targeted treatments are also summarized. The aim of the review is linking autophagy to thyroid cancer, so as to develop novel approaches to better control cancer progression.

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BRAF-activated WT1 contributes to cancer growth and regulates autophagy and apoptosis in papillary thyroid carcinoma

Cited by 11 publications

References 48 publications

Cytoskeletal activation of NHE1 regulates mechanosensitive cell volume adaptation and proliferation

Cytoskeletal activation of NHE1 regulates mechanosensitive cell volume adaptation and proliferation

The Role of Activation of PI3K/AKT/mTOR and RAF/MEK/ERK Pathways in Aggressive Pituitary Adenomas—New Potential Therapeutic Approach—A Systematic Review

The new insights into autophagy in thyroid cancer progression

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