scholarly journals Comparative mechanisms of cancer cell migration through 3D matrix and physiological microtracks

2015 ◽  
Vol 308 (6) ◽  
pp. C436-C447 ◽  
Author(s):  
Shawn P. Carey ◽  
Aniqua Rahman ◽  
Casey M. Kraning-Rush ◽  
Bethsabe Romero ◽  
Sahana Somasegar ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cancer Cell ◽  
Actin Polymerization ◽  
Cancer Metastasis ◽  
Type I Collagen ◽  
Type I ◽  
Cancer Cell Migration ◽  
Cytoskeletal Dynamics ◽  
3D Matrix ◽  
Context Specific

Tumor cell invasion through the stromal extracellular matrix (ECM) is a key feature of cancer metastasis, and understanding the cellular mechanisms of invasive migration is critical to the development of effective diagnostic and therapeutic strategies. Since cancer cell migration is highly adaptable to physiochemical properties of the ECM, it is critical to define these migration mechanisms in a context-specific manner. Although extensive work has characterized cancer cell migration in two- and three-dimensional (3D) matrix environments, the migration program employed by cells to move through native and cell-derived microtracks within the stromal ECM remains unclear. We previously reported the development of an in vitro model of patterned type I collagen microtracks that enable matrix metalloproteinase-independent microtrack migration. Here we show that collagen microtracks closely resemble channel-like gaps in native mammary stroma ECM and examine the extracellular and intracellular mechanisms underlying microtrack migration. Cell-matrix mechanocoupling, while critical for migration through 3D matrix, is not necessary for microtrack migration. Instead, cytoskeletal dynamics, including actin polymerization, cortical tension, and microtubule turnover, enable persistent, polarized migration through physiological microtracks. These results indicate that tumor cells employ context-specific mechanisms to migrate and suggest that selective targeting of cytoskeletal dynamics, but not adhesion, proteolysis, or cell traction forces, may effectively inhibit cancer cell migration through preformed matrix microtracks within the tumor stroma.

scholarly journals ELMO2 association with Gαi2 regulates pancreatic cancer cell chemotaxis and metastasis

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8910
Author(s):  
Yecheng Wang ◽  
Hongyan Li ◽  
Fei Li
Keyword(s):  
Pancreatic Cancer ◽  
Cell Migration ◽  
Cancer Cell ◽  
Actin Polymerization ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Migration ◽  
Pancreatic Cancer Cells ◽  
Cell Chemotaxis

Background Pancreatic cancer is a highly lethal disease. Nearly half of the patients have distant metastasis and remain asymptomatic. Emerging evidence suggests that the chemokine, CXCL12, has a role in cancer metastasis. The interaction between CXCL12 and CXCR4 activates heterotrimeric G proteins, which regulates actin polymerization and cancer cell migration. However, the molecular mechanisms underlying pancreatic cancer cell migration are still largely obscure. Here, we addressed the role of ELMO2 in chemotaxis and metastasis of pancreatic cancer cells. Methods Pancreatic cancer cell lines PANC-1 and AsPC-1 and siRNA-mediated knockdown of ELMO2 were used to determine the effects of ELMO2 on cancer cell chemotaxis, invasion, migration. Co-immunoprecipitation assays were carried out to identify interacting partners of ELMO2. Results ELMO2 knockdown inhibited pancreatic cancer cell chemotaxis, migration, invasion, and F-actin polymerization. Co-immunoprecipitation assays revealed that ELMO2 interacted with Gαi2 and that CXCL12 triggered Gα i2-dependent membrane translocation of ELMO2. Thus, ELMO2 is a potential therapeutic target for pancreatic cancer.

scholarly journals Uncovering the signaling landscape controlling breast cancer cell migration identifies splicing factor PRPF4B as a metastasis driver

2018 ◽  
Author(s):  
Michiel Fokkelman ◽  
Esmee Koedoot ◽  
Vasiliki-Maria Rogkoti ◽  
Sylvia E. Le Dévédec ◽  
Iris van de Sandt ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Metastasis ◽  
Breast Cancer Cell Lines ◽  
Cancer Cell Migration ◽  
Metastasis Formation ◽  
Breast Cancer Cell Migration ◽  
Basal Breast Cancer

AbstractMetastasis is the major cause of death in cancer patients and migration of cancer cells from the primary tumor to distant sites is the prerequisite of metastasis formation. Here we applied an imaging-based RNAi phenotypic cell migration screen using two highly migratory basal breast cancer cell lines (Hs578T and MDA-MB-231) to provide a repository for signaling determinants that functionally drive cancer cell migration. We screened ~4,200 individual target genes covering most cell signaling components and discovered 133 and 113 migratory modulators of Hs578T and MDA-MB-231, respectively, of which 43 genes were common denominators of cell migration. Interaction networks of candidate migratory modulators were in common with networks of different clinical breast cancer prognostic and metastasis classifiers. The splicing factors PRPF4B and BUD31 and the transcription factor BPTF were amplified in human primary breast tumors and the expression was associated with metastasis-free survival. Depletion of PRPF4B, BUD31 and BPTF caused primarily down-regulation of genes involved in focal adhesion and ECM-interaction pathways. PRPF4B was essential for triple negative breast cancer cell migration and critical for breast cancer metastasis formation in vivo, making PRPF4B a candidate for further drug development. Our systematic phenotypic screen provides an important repository of candidate metastasis drug targets.

Characterization of 3D matrix conditions for cancer cell migration with elasticity/porosity-independent tunable microfiber gels

2019 ◽  
Vol 52 (3) ◽  
pp. 333-344 ◽  
Author(s):  
Daoxiang Huang ◽  
Yu Nakamura ◽  
Aya Ogata ◽  
Satoru Kidoaki
Keyword(s):  
Cell Migration ◽  
Cancer Cell ◽  
Cancer Cell Migration ◽  
3D Matrix

ROCK-regulated cytoskeletal dynamics participate in the inhibitory effect of melatonin on cancer cell migration

2009 ◽  
Vol 46 (1) ◽  
pp. 15-21 ◽  
Author(s):  
Leonardo Ortíz-López ◽  
Sandra Morales-Mulia ◽  
Gerardo Ramírez-Rodríguez ◽  
Gloria Benítez-King
Keyword(s):  
Cell Migration ◽  
Cancer Cell ◽  
Inhibitory Effect ◽  
Cancer Cell Migration ◽  
Cytoskeletal Dynamics

scholarly journals Syndecan-1 facilitates breast cancer metastasis to the brain

2019 ◽  
Author(s):  
Megan R. Sayyad ◽  
Madhavi Puchalapalli ◽  
Natasha G. Vergara ◽  
Sierra Mosticone Wangensteen ◽  
Melvin Moore ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Brain Metastasis ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Cancer Cell Migration ◽  
The Brain

AbstractPurposeAlthough survival rates for patients with localized breast cancer have increased, patients with metastatic breast cancer still have poor prognosis. Understanding key factors involved in promoting breast cancer metastasis is imperative for better treatments. In this study, we investigated the role of syndecan-1 (Sdc1) in breast cancer metastasis.MethodsTo assess the role of Sdc1 in breast cancer metastasis, we silenced Sdc1 expression in the triple-negative breast cancer human MDA-MB-231 cell line and overexpressed it in the mouse mammary carcinoma 4T1 cell line. Intracardiac injections were performed in an experimental mouse metastasis model using both cell lines. In vitro transwell blood-brain barrier (BBB) and brain section adhesion assays were utilized to specifically investigate how Sdc1 promotes brain metastasis. A cytokine array was performed to evaluate differences in the breast cancer cell secretome when Sdc1 was silenced.ResultsSilencing expression of Sdc1 in breast cancer cells significantly reduced metastasis to the brain. Conversely, overexpression of Sdc1 increased metastasis to the brain. We found that the reduction in brain metastases with Sdc1 knockdown was likely due to reduced breast cancer cell migration across the BBB and adhesion to the perivascular regions of the brain. However, there was no change in attachment to brain endothelial cells or astrocytes. Loss of Sdc1 also led to changes in breast cancer cell-secreted cytokines, which may influence the BBB.ConclusionsTaken together, our study demonstrates a role for Sdc1 in promoting breast cancer metastasis to the brain. These findings suggest that Sdc1 supports breast cancer cell migration across the BBB through regulation of cytokines, which may modulate the BBB. Further elucidating this mechanism will allow for the development of therapeutic strategies to combat brain metastasis.

scholarly journals Suppressive Role of Androgen/Androgen Receptor Signaling via Chemokines on Prostate Cancer Cells

2019 ◽  
Vol 8 (3) ◽  
pp. 354 ◽  
Author(s):  
Kouji Izumi ◽  
Atsushi Mizokami
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Metastasis ◽  
Prostate Cancer Cell ◽  
Standard Form ◽  
Cancer Cell Migration ◽  
Prostate Cancer Cells

Androgen/androgen receptor (AR) signaling is a significant driver of prostate cancer progression, therefore androgen-deprivation therapy (ADT) is often used as a standard form of treatment for advanced and metastatic prostate cancer patients. However, after several years of ADT, prostate cancer progresses to castration-resistant prostate cancer (CRPC). Androgen/AR signaling is still considered an important factor for prostate cancer cell survival following CRPC progression, while recent studies have reported dichotomic roles for androgen/AR signaling. Androgen/AR signaling increases prostate cancer cell proliferation, while simultaneously inhibiting migration. As a result, ADT can induce prostate cancer metastasis. Several C-C motif ligand (CCL)-receptor (CCR) axes are involved in cancer cell migration related to blockade of androgen/AR signaling. The CCL2-CCR2 axis is negatively regulated by androgen/AR signaling, with the CCL22-CCR4 axis acting as a further downstream mediator, both of which promote prostate cancer cell migration. Furthermore, the CCL5-CCR5 axis inhibits androgen/AR signaling as an upstream mediator. CCL4 is involved in prostate carcinogenesis through macrophage AR signaling, while the CCL21-CCR7 axis in prostate cancer cells is activated by tumor necrotic factor, which is secreted when androgen/AR signaling is inhibited. Finally, the CCL2-CCR2 axis has recently been demonstrated to be a key contributor to cabazitaxel resistance in CRPC.

scholarly journals Protective Role of IRBIT on Sodium Bicarbonate Cotransporter-n1 for Migratory Cancer Cells

Pharmaceutics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 816
Author(s):  
Soyoung Hwang ◽  
Dong Min Shin ◽  
Jeong Hee Hong
Keyword(s):  
Cell Migration ◽  
Sodium Bicarbonate ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Metastasis ◽  
Specific Inhibitor ◽  
Protective Role ◽  
Cancer Cell Migration ◽  
Ip3 Receptor ◽  
Sodium Bicarbonate Cotransporter

IP3 receptor-binding protein released with IP3 (IRBIT) interacts with various ion channels and transporters. An electroneutral type of sodium bicarbonate cotransporter, NBCn1, participates in cell migration, and its enhanced expression is related to cancer metastasis. The effect of IRBIT on NBCn1 and its relation to cancer cell migration remain obscure. We therefore aimed to determine the effect of IRBIT on NBCn1 and the regulation of cancer cell migration due to IRBIT-induced alterations in NBCn1 activity. Overexpression of IRBIT enhanced cancer cell migration and NBC activity. Knockdown of IRBIT or NBCn1 and treatment with an NBC-specific inhibitor, S0859, attenuated cell migration. Stimulation with oncogenic epidermal growth factor enhanced the expression of NBCn1 and migration of cancer cells by recruiting IRBIT. The recruited IRBIT stably maintained the expression of the NBCn1 transporter machinery in the plasma membrane. Combined inhibition of IRBIT and NBCn1 dramatically inhibited the migration of cancer cells. Combined modulation of IRBIT and NBCn1 offers an effective strategy for attenuating cancer metastasis.

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