Piezo1 promoted hepatocellular carcinoma progression and EMT through activating TGF-β signaling by recruiting Rab5c

Li, Yiming; Xu, Cong; Sun, Bo; Zhong, Fang-Jing; Cao, Momo; Yang, Lian-Yue

doi:10.1186/s12935-022-02574-2

Cited by 19 publications

(11 citation statements)

References 71 publications

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Section: Discussionmentioning

confidence: 99%

“…PIEZO2 , IGFBP2 , and ACVR2A upregulation is associated with the promotion of EMT [ 96 , 97 , 98 , 99 , 100 , 101 ]. PIEZO2 (piezo-type mechanosensitive ion channel component 2) regulates the actin cytoskeleton, and actin remodeling can alter drug response [ 96 , 97 ]. IGFBP2 (insulin-like growth factor-binding protein 2) promotes cellular proliferation, and its upregulation correlates with chemotherapy resistance [ 98 , 99 , 100 ].…”

Section: Discussionmentioning

confidence: 99%

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Cellular Transcriptomics of Carboplatin Resistance in a Metastatic Canine Osteosarcoma Cell Line

Hodge

Miller

Weinman

et al. 2023

Genes

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Osteosarcoma prognosis has remained unchanged for the past three decades. In both humans and canines, treatment is limited to excision, radiation, and chemotherapy. Chemoresistance is the primary cause of treatment failure, and the trajectory of tumor evolution while under selective pressure from treatment is thought to be the major contributing factor in both species. We sought to understand the nature of platinum-based chemotherapy resistance by investigating cells that were subjected to repeated treatment and recovery cycles with increased carboplatin concentrations. Three HMPOS-derived cell lines, two resistant and one naïve, underwent single-cell RNA sequencing to examine transcriptomic perturbation and identify pathways leading to resistance and phenotypic changes. We identified the mechanisms of acquired chemoresistance and inferred the induced cellular trajectory that evolved with repeated exposure. The gene expression patterns indicated that acquired chemoresistance was strongly associated with a process similar to epithelial–mesenchymal transition (EMT), a phenomenon associated with the acquisition of migratory and invasive properties associated with metastatic disease. We conclude that the observed trajectory of tumor adaptability is directly correlated with chemoresistance and the phase of the EMT-like phenotype is directly affected by the level of chemoresistance. We infer that the EMT-like phenotype is a critical component of tumor evolution under treatment pressure and is vital to understanding the mechanisms of chemoresistance and to improving osteosarcoma prognosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cellular Transcriptomics of Carboplatin Resistance in a Metastatic Canine Osteosarcoma Cell Line

Hodge

Miller

Weinman

et al. 2023

Genes

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“…Several studies have shown that Piezo1 can help tumor cell metastasis by promoting EMT ( Gao et al, 2021 ; Wang et al, 2021 ). Piezo1 induces EMT by activating the TGF-β/Smad2/3 signaling pathway through the recruitment of Rab5c ( Li et al, 2022d ). Knockdown of Piezo1 transformes the HCCs from a spindle-like literal morphology to a cobblestone-like epithelial morphology, with a decreased ability of cells to migrate, and the growth of subcutaneous and orthotopic xenograft tumors was also inhibited ( Li et al, 2022d ).…”

Section: Association Of Piezo1 With Tumorsmentioning

confidence: 99%

“…Piezo1 induces EMT by activating the TGF-β/Smad2/3 signaling pathway through the recruitment of Rab5c ( Li et al, 2022d ). Knockdown of Piezo1 transformes the HCCs from a spindle-like literal morphology to a cobblestone-like epithelial morphology, with a decreased ability of cells to migrate, and the growth of subcutaneous and orthotopic xenograft tumors was also inhibited ( Li et al, 2022d ). Moreover, Piezo1 also promotes tumor metastasis by activating the non-Smad pathway of TGF-β.…”

Section: Association Of Piezo1 With Tumorsmentioning

confidence: 99%

Pleiotropic physiological functions of Piezo1 in human body and its effect on malignant behavior of tumors

Zhang,

Zou,

Dou

et al. 2024

Front. Physiol.

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Mechanosensitive ion channel protein 1 (Piezo1) is a large homotrimeric membrane protein. Piezo1 has various effects and plays an important and irreplaceable role in the maintenance of human life activities and homeostasis of the internal environment. In addition, recent studies have shown that Piezo1 plays a vital role in tumorigenesis, progression, malignancy and clinical prognosis. Piezo1 is involved in regulating the malignant behaviors of a variety of tumors, including cellular metabolic reprogramming, unlimited proliferation, inhibition of apoptosis, maintenance of stemness, angiogenesis, invasion and metastasis. Moreover, Piezo1 regulates tumor progression by affecting the recruitment, activation, and differentiation of multiple immune cells. Therefore, Piezo1 has excellent potential as an anti-tumor target. The article reviews the diverse physiological functions of Piezo1 in the human body and its major cellular pathways during disease development, and describes in detail the specific mechanisms by which Piezo1 affects the malignant behavior of tumors and its recent progress as a new target for tumor therapy, providing new perspectives for exploring more potential effects on physiological functions and its application in tumor therapy.

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“…In liver cancer, Piezo1 is directly correlated with poor clinical outcomes. Piezo1 recruits Rab5c, a small GTPase, promoting hepatocellular carcinoma via TGF-β signaling [ 117 ]. Additionally, Piezo1 is necessary for MAPK and YAP activation and translocation in hepatocellular carcinoma through an independent Hippo signaling mechanism [ 118 ].…”

Section: Mechanoreceptors In Cancermentioning

confidence: 99%

Mechanosensitive Ion Channels: Their Physiological Importance and Potential Key Role in Cancer

Otero-Sobrino,

Blanco-Carlón,

Navarro-Aguadero

et al. 2023

IJMS

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Mechanosensitive ion channels comprise a broad group of proteins that sense mechanical extracellular and intracellular changes, translating them into cation influx to adapt and respond to these physical cues. All cells in the organism are mechanosensitive, and these physical cues have proven to have an important role in regulating proliferation, cell fate and differentiation, migration and cellular stress, among other processes. Indeed, the mechanical properties of the extracellular matrix in cancer change drastically due to high cell proliferation and modification of extracellular protein secretion, suggesting an important contribution to tumor cell regulation. In this review, we describe the physiological significance of mechanosensitive ion channels, emphasizing their role in cancer and immunity, and providing compelling proof of the importance of continuing to explore their potential as new therapeutic targets in cancer research.

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Piezo1 promoted hepatocellular carcinoma progression and EMT through activating TGF-β signaling by recruiting Rab5c

Cited by 19 publications

References 71 publications

Cellular Transcriptomics of Carboplatin Resistance in a Metastatic Canine Osteosarcoma Cell Line

Cellular Transcriptomics of Carboplatin Resistance in a Metastatic Canine Osteosarcoma Cell Line

Pleiotropic physiological functions of Piezo1 in human body and its effect on malignant behavior of tumors

Mechanosensitive Ion Channels: Their Physiological Importance and Potential Key Role in Cancer

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