Laminin‐derived peptide C16 regulates Tks expression and reactive oxygen species generation in human prostate cancer cells

Caires-Dos-Santos, Livia; Silva, Suély V. da; Smuczek, Basilio; Siqueira, Adriane Sousa de; Cruz, Karen Steponavicius Piedade; Barbuto, José Alexandre Marzagão; Augusto, Taize Machado; Freitas, Vanessa M.; Carvalho, Hernandes F.; Jaeger, Ruy Gastaldoni

doi:10.1002/jcp.28997

Cited by 13 publications

(11 citation statements)

References 48 publications

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“…A contribution of Tks4 to cancer progression has been suggested in several cancer types, including breast cancer [53], melanoma [27], acute myeloid leukemia [54], and prostate cancer [55]. Consistent with these links, a detailed analysis showed that Tks4 and its phosphorylation are implicated in invadopodia formation in human colon cancer cells [56].…”

Section: Discussionmentioning

confidence: 85%

Absence of the Tks4 Scaffold Protein Induces Epithelial-Mesenchymal Transition-Like Changes in Human Colon Cancer Cells

Szeder

Tarnoki-Zach

Lakatos

et al. 2019

Cells

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Epithelial to mesenchymal transition (EMT) is a multipurpose process involved in wound healing, development, and certain pathological processes, such as metastasis formation. The Tks4 scaffold protein has been implicated in cancer progression; however, its role in oncogenesis is not well defined. In this study, the function of Tks4 was investigated in HCT116 colon cancer cells by knocking the protein out using the CRISPR/Cas9 system. Surprisingly, the absence of Tks4 induced significant changes in cell morphology, motility, adhesion and expression, and localization of E-cadherin, which are all considered as hallmarks of EMT. In agreement with these findings, the marked appearance of fibronectin, a marker of the mesenchymal phenotype, was also observed in Tks4-KO cells. Analysis of the expression of well-known EMT transcription factors revealed that Snail2 was strongly overexpressed in cells lacking Tks4. Tks4-KO cells showed increased motility and decreased cell–cell attachment. Collagen matrix invasion assays demonstrated the abundance of invasive solitary cells. Finally, the reintroduction of Tks4 protein in the Tks4-KO cells restored the expression levels of relevant key transcription factors, suggesting that the Tks4 scaffold protein has a specific and novel role in EMT regulation and cancer progression.

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Section: Discussionmentioning

confidence: 85%

Absence of the Tks4 Scaffold Protein Induces Epithelial-Mesenchymal Transition-Like Changes in Human Colon Cancer Cells

Szeder

Tarnoki-Zach

Lakatos

et al. 2019

Cells

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“…It was suspected that TKS proteins, which are members of the same family, can also play regulatory roles in channeling and localizing the NOX enzymes to the podosome/invadopodium membrane to locally increase the ROS concentration [65,146]. TKS5 has been shown to colocalize with ROS [147]. Furthermore, Diaz et al…”

Section: The Possible Role Of Tks4 and Tks5 In The Compartmentalization Of Oxidative Processesmentioning

confidence: 99%

Advances in Understanding TKS4 and TKS5: Molecular Scaffolds Regulating Cellular Processes from Podosome and Invadopodium Formation to Differentiation and Tissue Homeostasis

Kudlik

Takács

Radnai

et al. 2020

IJMS

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Scaffold proteins are typically thought of as multi-domain “bridging molecules.” They serve as crucial regulators of key signaling events by simultaneously binding multiple participants involved in specific signaling pathways. In the case of epidermal growth factor (EGF)-epidermal growth factor receptor (EGFR) binding, the activated EGFR contacts cytosolic SRC tyrosine-kinase, which then becomes activated. This process leads to the phosphorylation of SRC-substrates, including the tyrosine kinase substrates (TKS) scaffold proteins. The TKS proteins serve as a platform for the recruitment of key players in EGFR signal transduction, promoting cell spreading and migration. The TKS4 and the TKS5 scaffold proteins are tyrosine kinase substrates with four or five SH3 domains, respectively. Their structural features allow them to recruit and bind a variety of signaling proteins and to anchor them to the cytoplasmic surface of the cell membrane. Until recently, TKS4 and TKS5 had been recognized for their involvement in cellular motility, reactive oxygen species-dependent processes, and embryonic development, among others. However, a number of novel functions have been discovered for these molecules in recent years. In this review, we attempt to cover the diverse nature of the TKS molecules by discussing their structure, regulation by SRC kinase, relevant signaling pathways, and interaction partners, as well as their involvement in cellular processes, including migration, invasion, differentiation, and adipose tissue and bone homeostasis. We also describe related pathologies and the established mouse models.

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“…Prostate cancer remains a major cause of mortality annually among males [1][2][3][4][5][6]. In 2015, prostate cancer was the fifth commonly diagnosed cancer in South Korea and it is expected to become the fourth in 2019 [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Evodiamine Mitigates Cellular Growth and Promotes Apoptosis by Targeting the c-Met Pathway in Prostate Cancer Cells

Hwang

Chinnathambi

et al. 2020

Molecules

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Evodiamine (EVO) is an indoloquinazoline alkaloid that exerts its various anti-oncogenic actions by blocking phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), mitogen-activated protein kinase (MAPK), c-Met, and nuclear factor kappa B (NF-κB) signaling pathways, thus leading to apoptosis of tumor cells. We investigated the ability of EVO to affect hepatocyte growth factor (HGF)-induced c-Met/Src/STAT3 activation cascades in castration-resistant prostate cancer (CRPC). First, we noted that EVO showed cytotoxicity and anti-proliferation activities in PC-3 and DU145 cells. Next, we found that EVO markedly inhibited HGF-induced c-Met/Src/STAT3 phosphorylation and impaired the nuclear translocation of STAT3 protein. Then, we noted that EVO arrested the cell cycle, caused apoptosis, and downregulated the expression of various carcinogenic markers such as B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), cyclin D1, cyclooxygenase 2 (COX-2), survivin, vascular endothelial growth factor (VEGF), and matrix metallopeptidases 9 (MMP-9). Moreover, it was observed that in cPC-3 and DU145 cells transfected with c-Met small interfering RNA (siRNA), Src/STAT3 activation was also mitigated and led to a decrease in EVO-induced apoptotic cell death. According to our results, EVO can abrogate the activation of the c-Met/Src/STAT3 signaling axis and thus plays a role as a robust suppressor of tumor cell survival, proliferation, and angiogenesis.

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Laminin‐derived peptide C16 regulates Tks expression and reactive oxygen species generation in human prostate cancer cells

Cited by 13 publications

References 48 publications

Absence of the Tks4 Scaffold Protein Induces Epithelial-Mesenchymal Transition-Like Changes in Human Colon Cancer Cells

Absence of the Tks4 Scaffold Protein Induces Epithelial-Mesenchymal Transition-Like Changes in Human Colon Cancer Cells

Advances in Understanding TKS4 and TKS5: Molecular Scaffolds Regulating Cellular Processes from Podosome and Invadopodium Formation to Differentiation and Tissue Homeostasis

Evodiamine Mitigates Cellular Growth and Promotes Apoptosis by Targeting the c-Met Pathway in Prostate Cancer Cells

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