invasive phenotype
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2022 ◽  
Vol 16 ◽  
pp. 101320
Rama Kadamb ◽  
Boris A Leibovitch ◽  
Eduardo F Farias ◽  
Nisha Dahiya ◽  
Hemant Suryawanshi ◽  

2022 ◽  
Vol 23 (1) ◽  
Mingzhi Luo ◽  
Grace Cai ◽  
Kenneth K. Y. Ho ◽  
Kang Wen ◽  
Zhaowen Tong ◽  

Abstract Background Uncontrolled growth in solid breast cancer generates mechanical compression that may drive the cancer cells into a more invasive phenotype, but little is known about how such compression affects the key events and corresponding regulatory mechanisms associated with invasion of breast cancer cells including cellular behaviors and matrix degradation. Results Here we show that compression enhanced invasion and matrix degradation of breast cancer cells. We also identified Piezo1 as the putative mechanosensitive cellular component that transmitted compression to not only enhance the invasive phenotype, but also induce calcium influx and downstream Src signaling. Furthermore, we demonstrated that Piezo1 was mainly localized in caveolae, and both Piezo1 expression and compression-enhanced invasive phenotype of the breast cancer cells were reduced when caveolar integrity was compromised by either knocking down caveolin1 expression or depleting cholesterol content. Conclusions Taken together, our data indicate that mechanical compression activates Piezo1 channels to mediate enhanced breast cancer cell invasion, which involves both cellular events and matrix degradation. This may be a critical mechanotransduction pathway during breast cancer metastasis, and thus potentially a novel therapeutic target for the disease.

Life ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1294
Taoufik Nedjadi ◽  
Nada Albarakati ◽  
Hicham Benabdelkamel ◽  
Afshan Masood ◽  
Assim A. Alfadda ◽  

Background: Bladder cancer is a life-threatening disease and a major cause of cancer-associated complications. The main challenges confronted during the clinical management of bladder cancer are associated with recurrence and disease progression to the muscle-invasive phenotype. Improved early detection of the disease is of paramount importance to prevent disease progression and improve survival. Hence, novel clinically applicable biomarkers for early detection are warranted. Methods: In the current study, a comparative proteomic approach was undertaken using plasma samples to identify protein biomarkers associated with the muscle-invasive phenotype of bladder carcinoma. Isolated plasma proteins were depleted, DIGE-labeled, then subjected to conventional 2D electrophoresis followed by mass spectrometry for identification of differentially expressed proteins. Western blot was used for data validation. Results: Fourteen differentially expressed proteins with statistically significant changes in abundance between the cancer group and control group were identified. Three differentially expressed proteins were selected for validation, among which apolipoprotein A1 exhibited high specificity and sensitivity (AUC = 0.906). Ingenuity pathway analysis identified IFN-γ and TNF-α as the main signaling hub for the differentially regulated proteins. Conclusion: Our findings provide additional insight into understanding bladder cancer pathogenesis. Our data identified potential non-invasive plasma-derived biomarker proteins that merit additional investigation to validate its clinical usefulness to prevent bladder cancer progression.

Patrycja Przygodzka ◽  
Ewelina Sochacka ◽  
Kamila Soboska ◽  
Marcin Pacholczyk ◽  
Izabela Papiewska-Pająk ◽  

Abstract Background Successful colorectal cancer (CRC) therapy often depends on the accurate identification of primary tumours with invasive potential. There is still a lack of identified pathological factors associated with disease recurrence that could help in making treatment decisions. Neuromedin U (NMU) is a secretory neuropeptide that was first isolated from the porcine spinal cord, and it has emerged as a novel factor involved in the tumorigenesis and/or metastasis of many types of cancers. Previously associated with processes leading to CRC cell invasiveness, NMU has the potential to be a marker of poor outcome, but it has not been extensively studied in CRC. Methods Data from The Cancer Genome Atlas (TCGA) were used to analyse NMU and NMU receptor (NMUR1 and NMUR2) expression in CRC tissues vs. normal tissues, and real-time PCR was used for NMU and NMU receptor expression analysis. NMU protein detection was performed by immunoblotting. Secreted NMU was immunoprecipitated from cell culture-conditioned media and analysed by immunoblotting and protein sequencing. DNA demethylation by 5-aza-CdR was used to analyse the regulation of NMUR1 and NMUR2 expression. NMU receptor activity was monitored by detecting calcium mobilisation in cells loaded with fluo-4, and ERK1/2 kinase activation was detected after treatment with NMU or receptor agonist. Cell migration and invasion were investigated using membrane filters. Integrin expression was evaluated by flow cytometry. Results The obtained data revealed elevated expression of NMU and NMUR2 in CRC tissue samples and variable expression in the analysed CRC cell lines. We have shown, for the first time, that NMUR2 activation induces signalling in CRC cells and that NMU increases the motility and invasiveness of NMUR2-positive CRC cells and increases prometastatic integrin receptor subunit expression. Conclusions Our results show the ability of CRC cells to respond to NMU via activation of the NMUR2 receptor, which ultimately leads to a shift in the CRC phenotype towards a more invasive phenotype.

iScience ◽  
2021 ◽  
pp. 102935
Heber L. Rocha ◽  
Ineˆs Godet ◽  
Furkan Kurtoglu ◽  
John Metzcar ◽  
Kali Konstantinopoulos ◽  

2021 ◽  
Haider Tari ◽  
Ketty Kessler ◽  
Nicholas Trahearn ◽  
Benjamin Werner ◽  
Maria Vinci ◽  

AbstractIntra-tumour heterogeneity is an intrinsic property of all cancers. In some cases, such variation can be maintained by interactions between tumour subclones with distinct molecular and phenotypic characteristics. In paediatric gliomas, interactions can take the form of enhanced invasive phenotype, a hallmark of these malignancies. However, subclonal interactions are hard to quantify and difficult to distinguish from spatial confounding factors and experimental bias. Here we combine spatial computational modelling of cellular interactions and invasion, with co-evolution experiments of clonally disassembled primary glioma lines derived at autopsy. We design a Bayesian inference framework to quantify spatial subclonal interactions between molecular and phenotypically distinct lineages with different patterns of invasion. We show how this approach could discriminate genuine subclonal interactions where one clone enhanced the invasive phenotype of another, from apparent interactions that were only due to the complex dynamics of subclones growing in space. This study provides a new approach for the identification and quantification of spatial subclonal interactions in cancer.

2021 ◽  
Vol 22 (11) ◽  
pp. 6161
Chinmayee Dash ◽  
Tanmoy Saha ◽  
Shiladitya Sengupta ◽  
Hae Lin Jang

The interaction of tumor cells with blood vessels is one of the key steps during cancer metastasis. Metastatic cancer cells exhibit phenotypic state changes during this interaction: (1) they form tunneling nanotubes (TNTs) with endothelial cells, which act as a conduit for intercellular communication; and (2) metastatic cancer cells change in order to acquire an elongated phenotype, instead of the classical cellular aggregates or mammosphere-like structures, which it forms in three-dimensional cultures. Here, we demonstrate mechanistically that a siRNA-based knockdown of the exocyst complex protein Sec3 inhibits TNT formation. Furthermore, a set of pharmacological inhibitors for Rho GTPase–exocyst complex-mediated cytoskeletal remodeling is introduced, which inhibits TNT formation, and induces the reversal of the more invasive phenotype of cancer cell (spindle-like) into a less invasive phenotype (cellular aggregates or mammosphere). Our results offer mechanistic insights into this nanoscale communication and shift of phenotypic state during cancer–endothelial interactions.

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