scholarly journals STIM1- and Orai1-mediated Ca2+ oscillation orchestrates invadopodium formation and melanoma invasion

2014 ◽  
Vol 207 (4) ◽  
pp. 535-548 ◽  
Author(s):  
Jianwei Sun ◽  
Fujian Lu ◽  
Huifang He ◽  
Junling Shen ◽  
Jane Messina ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Plasma Membrane ◽  
Mouse Model ◽  
Matrix Metalloproteinase ◽  
Cell Invasion ◽  
Cancer Cell Invasion ◽  
Invasion And Metastasis ◽  
Melanoma Invasion ◽  
Ecm Degradation ◽  
Underlying Mechanisms

Ca2+ signaling has been increasingly implicated in cancer invasion and metastasis, and yet, the underlying mechanisms remained largely unknown. In this paper, we report that STIM1- and Orai1-mediated Ca2+ oscillations promote melanoma invasion by orchestrating invadopodium assembly and extracellular matrix (ECM) degradation. Ca2+ oscillation signals facilitate invadopodial precursor assembly by activating Src. Disruption of Ca2+ oscillations inhibited invadopodium assembly. Furthermore, STIM1 and Orai1 regulate the proteolysis activity of individual invadopodia. Mechanistically, Orai1 blockade inhibited the recycling of MT1–matrix metalloproteinase (MMP) to the plasma membrane and entrapped MT1-MMP in the endocytic compartment to inhibit ECM degradation. STIM1 knockdown significantly inhibited melanoma lung metastasis in a xenograft mouse model, implicating the importance of this pathway in metastatic dissemination. Our findings provide a novel mechanism for Ca2+-mediated cancer cell invasion and shed new light on the spatiotemporal organization of store-operated Ca2+ signals during melanoma invasion and metastasis.

scholarly journals Ultraviolet light-induced collagen degradation inhibits melanoma invasion

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Timothy Budden ◽  
Caroline Gaudy-Marqueste ◽  
Andrew Porter ◽  
Emily Kay ◽  
Shilpa Gurung ◽  
...  
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Cancer Cells ◽  
Cell Invasion ◽  
Collagen Synthesis ◽  
Dermal Fibroblast ◽  
Single Cells ◽  
Invasive Front ◽  
Melanoma Invasion ◽  
Ecm Degradation

AbstractUltraviolet radiation (UVR) damages the dermis and fibroblasts; and increases melanoma incidence. Fibroblasts and their matrix contribute to cancer, so we studied how UVR modifies dermal fibroblast function, the extracellular matrix (ECM) and melanoma invasion. We confirmed UVR-damaged fibroblasts persistently upregulate collagen-cleaving matrix metalloprotein-1 (MMP1) expression, reducing local collagen (COL1A1), and COL1A1 degradation by MMP1 decreased melanoma invasion. Conversely, inhibiting ECM degradation and MMP1 expression restored melanoma invasion. Primary cutaneous melanomas of aged humans show more cancer cells invade as single cells at the invasive front of melanomas expressing and depositing more collagen, and collagen and single melanoma cell invasion are robust predictors of poor melanoma-specific survival. Thus, primary melanomas arising over collagen-degraded skin are less invasive, and reduced invasion improves survival. However, melanoma-associated fibroblasts can restore invasion by increasing collagen synthesis. Finally, high COL1A1 gene expression is a biomarker of poor outcome across a range of primary cancers.

scholarly journals Quantitative real-time imaging of molecular dynamics during cancer cell invasion and metastasis in vivo

2009 ◽  
Vol 3 (4) ◽  
pp. 351-354 ◽  
Author(s):  
Paul Timpson ◽  
Alan Serrels ◽  
Marta Canel ◽  
Margaret C. Frame ◽  
Valerie G. Brunton ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Real Time ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Cancer Cell Invasion ◽  
Invasion And Metastasis ◽  
Real Time Imaging

scholarly journals The activity status of cofilin is directly related to invasion, intravasation, and metastasis of mammary tumors

2006 ◽  
Vol 173 (3) ◽  
pp. 395-404 ◽  
Author(s):  
Weigang Wang ◽  
Ghassan Mouneimne ◽  
Mazen Sidani ◽  
Jeffrey Wyckoff ◽  
Xiaoming Chen ◽  
...  
Keyword(s):  
Cell Motility ◽  
Cell Invasion ◽  
Actin Polymerization ◽  
Cancer Cell Invasion ◽  
Invasion And Metastasis ◽  
Over Expression ◽  
Cell Biol ◽  
Tumor Cell Motility ◽  
New Strategies

Understanding the mechanisms controlling cancer cell invasion and metastasis constitutes a fundamental step in setting new strategies for diagnosis, prognosis, and therapy of metastatic cancers. LIM kinase1 (LIMK1) is a member of a novel class of serine–threonine protein kinases. Cofilin, a LIMK1 substrate, is essential for the regulation of actin polymerization and depolymerization during cell migration. Previous studies have made opposite conclusions as to the role of LIMK1 in tumor cell motility and metastasis, claiming either an increase or decrease in cell motility and metastasis as a result of LIMK1 over expression (Zebda, N., O. Bernard, M. Bailly, S. Welti, D.S. Lawrence, and J.S. Condeelis. 2000. J. Cell Biol. 151:1119–1128; Davila, M., A.R. Frost, W.E. Grizzle, and R. Chakrabarti. 2003. J. Biol. Chem. 278:36868–36875; Yoshioka, K., V. Foletta, O. Bernard, and K. Itoh. 2003. Proc. Natl. Acad. Sci. USA. 100:7247–7252; Nishita, M., C. Tomizawa, M. Yamamoto, Y. Horita, K. Ohashi, and K. Mizuno. 2005. J. Cell Biol. 171:349–359). We resolve this paradox by showing that the effects of LIMK1 expression on migration, intravasation, and metastasis of cancer cells can be most simply explained by its regulation of the output of the cofilin pathway. LIMK1-mediated decreases or increases in the activity of the cofilin pathway are shown to cause proportional decreases or increases in motility, intravasation, and metastasis of tumor cells.

scholarly journals Suppression of death receptor 5 enhances cancer cell invasion and metastasis through activation of caspase-8/TRAF2-mediated signaling

Oncotarget ◽  
2015 ◽  
Vol 6 (38) ◽  
pp. 41324-41338 ◽  
Author(s):  
You-Take Oh ◽  
Ping Yue ◽  
Dongsheng Wang ◽  
Jing-Shan Tong ◽  
Zhuo G. Chen ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Cell Invasion ◽  
Death Receptor ◽  
Caspase 8 ◽  
Death Receptor 5 ◽  
Cancer Cell Invasion ◽  
Invasion And Metastasis

scholarly journals The Role of WAVE2 Signaling in Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1217
Author(s):  
Priyanka Shailendra Rana ◽  
Akram Alkrekshi ◽  
Wei Wang ◽  
Vesna Markovic ◽  
Khalid Sossey-Alaoui
Keyword(s):  
Actin Cytoskeleton ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Critical Role ◽  
Therapeutic Strategies ◽  
Small Gtpases ◽  
Cancer Cell Invasion ◽  
Invasion And Metastasis ◽  
Regulatory Complex

The Wiskott–Aldrich syndrome protein (WASP) and WASP family verprolin-homologous protein (WAVE)—WAVE1, WAVE2 and WAVE3 regulate rapid reorganization of cortical actin filaments and have been shown to form a key link between small GTPases and the actin cytoskeleton. Upon receiving upstream signals from Rho-family GTPases, the WASP and WAVE family proteins play a significant role in polymerization of actin cytoskeleton through activation of actin-related protein 2/3 complex (Arp2/3). The Arp2/3 complex, once activated, forms actin-based membrane protrusions essential for cell migration and cancer cell invasion. Thus, by activation of Arp2/3 complex, the WAVE and WASP family proteins, as part of the WAVE regulatory complex (WRC), have been shown to play a critical role in cancer cell invasion and metastasis, drawing significant research interest over recent years. Several studies have highlighted the potential for targeting the genes encoding either part of or a complete protein from the WASP/WAVE family as therapeutic strategies for preventing the invasion and metastasis of cancer cells. WAVE2 is well documented to be associated with the pathogenesis of several human cancers, including lung, liver, pancreatic, prostate, colorectal and breast cancer, as well as other hematologic malignancies. This review focuses mainly on the role of WAVE2 in the development, invasion and metastasis of different types of cancer. This review also summarizes the molecular mechanisms that regulate the activity of WAVE2, as well as those oncogenic pathways that are regulated by WAVE2 to promote the cancer phenotype. Finally, we discuss potential therapeutic strategies that target WAVE2 or the WAVE regulatory complex, aimed at preventing or inhibiting cancer invasion and metastasis.

scholarly journals Overexpressed hPTTG1 promotes breast cancer cell invasion and metastasis by regulating GEF-H1/RhoA signalling

Oncogene ◽  
2011 ◽  
Vol 31 (25) ◽  
pp. 3086-3097 ◽  
Author(s):  
Y C Liao ◽  
J W Ruan ◽  
I Lua ◽  
M H Li ◽  
W L Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cell Invasion ◽  
Cancer Cell Invasion ◽  
Invasion And Metastasis ◽  
Breast Cancer Cell Invasion
Sign in / Sign up

Export Citation Format

Share Document