scholarly journals Extracellular Matrix Signals as Drivers of Mitochondrial Bioenergetics and Metabolic Plasticity of Cancer Cells During Metastasis

2021 ◽  
Vol 9 ◽  
Author(s):  
Félix A. Urra ◽  
Sebastián Fuentes-Retamal ◽  
Charlotte Palominos ◽  
Yarcely A. Rodríguez-Lucart ◽  
Camila López-Torres ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cancer Cells ◽  
Rho Gtpases ◽  
Therapeutic Potential ◽  
Mitochondrial Metabolism ◽  
Migration And Invasion ◽  
Mitochondrial Bioenergetics ◽  
Atp Production ◽  
Metabolic Plasticity

The role of metabolism in tumor growth and chemoresistance has received considerable attention, however, the contribution of mitochondrial bioenergetics in migration, invasion, and metastasis is recently being understood. Migrating cancer cells adapt their energy needs to fluctuating changes in the microenvironment, exhibiting high metabolic plasticity. This occurs due to dynamic changes in the contributions of metabolic pathways to promote localized ATP production in lamellipodia and control signaling mediated by mitochondrial reactive oxygen species. Recent evidence has shown that metabolic shifts toward a mitochondrial metabolism based on the reductive carboxylation, glutaminolysis, and phosphocreatine-creatine kinase pathways promote resistance to anoikis, migration, and invasion in cancer cells. The PGC1a-driven metabolic adaptations with increased electron transport chain activity and superoxide levels are essential for metastasis in several cancer models. Notably, these metabolic changes can be determined by the composition and density of the extracellular matrix (ECM). ECM stiffness, integrins, and small Rho GTPases promote mitochondrial fragmentation, mitochondrial localization in focal adhesion complexes, and metabolic plasticity, supporting enhanced migration and metastasis. Here, we discuss the role of ECM in regulating mitochondrial metabolism during migration and metastasis, highlighting the therapeutic potential of compounds affecting mitochondrial function and selectively block cancer cell migration.

scholarly journals Differential regulation of rho GTPases during lung adenocarcinoma migration and invasion reveals a novel role of the tumor suppressor StarD13 in invadopodia regulation

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Maria Al Haddad ◽  
Rayane El-Rif ◽  
Samer Hanna ◽  
Leila Jaafar ◽  
Rayanne Dennaoui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Rho Gtpases ◽  
Normal Lung ◽  
Migration And Invasion ◽  
Lung Cells ◽  
Invadopodia Formation

Abstract Background Lung cancer is the second most commonly occurring cancer. The ability to metastasize and spread to distant locations renders the tumor more aggressive. Members of the Rho subfamily of small GTP-binding proteins (GTPases) play a central role in the regulation of the actin cytoskeleton and in cancer cell migration and metastasis. In this study we investigated the role of the RhoA/Cdc42 GAP, StarD13, a previously described tumor suppressor, in malignancy, migration and invasion of the lung cancer cells A549. Methods We knocked down StarD13 expression in A549 lung cancer cells and tested the effect on cell migration and invadopodia formation using time lapse imaging and invasion assays. We also performed rescue experiments to determine the signaling pathways downstream of StarD13 and transfected the cells with FRET biosensors for RhoGTPases to identify the proteins involved in invadopodia formation. Results We observed a decrease in the level of expression of StarD13 in lung tumor tissues compared to normal lung tissues through immunohistochemistry. StarD13 also showed a lower expression in the lung adenocarcinoma cell line A549 compared to normal lung cells, WI38. In addition, the depletion of StarD13 increased cell proliferation and viability in WI38 and A549 cells, suggesting that StarD13 might potentially be a tumor suppressor in lung cancer. The depletion of StarD13, however, inhibited cell motility, conversely demonstrating a positive regulatory role in cell migration. This was potentially due to the constitutive activation of RhoA detected by pull down and FRET assays. Surprisingly, StarD13 suppressed cell invasion by inhibiting Cdc42-mediated invadopodia formation. Indeed, TKS4 staining and invadopodia assay revealed that StarD13 depletion increased Cdc42 activation as well as invadopodia formation and matrix degradation. Normal lung cells depleted of StarD13 also produced invadopodia, otherwise a unique hallmark of invasive cancer cells. Cdc42 knock down mimicked the effects of StarD13, while overexpression of a constitutively active Cdc42 mimicked the effects of its depletion. Finally, immunostaining and FRET analysis revealed the absence of StarD13 in invadopodia as compared to Cdc42, which was activated in invadopodia at the sites of matrix degradation. Conclusion In conclusion, StarD13 plays distinct roles in lung cancer cell migration and invasion through its differential regulation of Rho GTPases.

scholarly journals Highly expressed SLCO1B3 inhibits the occurrence and development of breast cancer and can be used as a clinical indicator of prognosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tiantian Tang ◽  
Guiying Wang ◽  
Sihua Liu ◽  
Zhaoxue Zhang ◽  
Chen Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines

AbstractThe role of organic anion transporting polypeptide 1B3 (SLCO1B3) in breast cancer is still controversial. The clinical immunohistochemical results showed that a greater proportion of patients with negative lymph nodes, AJCC stage I, and histological grade 1 (P < 0.05) was positively correlated with stronger expression of SLCO1B3, and DFS and OS were also increased significantly in these patients (P = 0.041, P = 0.001). Further subgroup analysis showed that DFS and OS were significantly enhanced with the increased expression of SLCO1B3 in the ER positive subgroup. The cellular function assay showed that the ability of cell proliferation, migration and invasion was significantly enhanced after knockdown of SLCO1B3 expression in breast cancer cell lines. In contrast, the ability of cell proliferation, migration and invasion was significantly reduced after overexpress the SLCO1B3 in breast cancer cell lines (P < 0.05). Overexpression or knockdown of SLCO1B3 had no effect on the apoptotic ability of breast cancer cells. High level of SLCO1B3 expression can inhibit the proliferation, invasion and migration of breast cancer cells, leading to better prognosis of patients. The role of SLCO1B3 in breast cancer may be related to estrogen. SLCO1B3 will become a potential biomarker for breast cancer diagnosis and prognosis assessment.

scholarly journals Emerging roles of cancer-testis antigenes, semenogelin 1 and 2, in neoplastic cells

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Oleg Shuvalov ◽  
Alyona Kizenko ◽  
Alexey Petukhov ◽  
Olga Fedorova ◽  
Alexandra Daks ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Reproductive System ◽  
Seminal Fluid ◽  
Cancer Development ◽  
Migration And Invasion ◽  
Malignant Cells ◽  
Cancer Testis

AbstractCancer-testicular Antigens (CTAs) belong to a group of proteins that under normal conditions are strictly expressed in a male’s reproductive tissues. However, upon malignisation, they are frequently re-expressed in neoplastic tissues of various origin. A number of studies have shown that different CTAs affect growth, migration and invasion of tumor cells and favor cancer development and metastasis. Two members of the CTA group, Semenogelin 1 and 2 (SEMG1 and SEMG2, or SEMGs) represent the major component of human seminal fluid. They regulate the motility and capacitation of sperm. They are often re-expressed in different malignancies including breast cancer. However, there is almost no information about the functional properties of SEMGs in cancer cells. In this review, we highlight the role of SEMGs in the reproductive system and also summarize the data on their expression and functions in malignant cells of various origins.

scholarly journals The Role of Multicellular Aggregation in the Survival of ErbB2-positive Breast Cancer Cells during Extracellular Matrix Detachment

2015 ◽  
Vol 290 (14) ◽  
pp. 8722-8733 ◽  
Author(s):  
Raju R. Rayavarapu ◽  
Brendan Heiden ◽  
Nicholas Pagani ◽  
Melissa M. Shaw ◽  
Sydney Shuff ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Positive Breast Cancer

scholarly journals Dysregulation of Transcription Factor EB Contributes to Cell Proliferation, Metastasis and Stemness in Breast Cancer

2021 ◽  
Author(s):  
Ningwei Fu ◽  
Ning Fan ◽  
Wenchao Luo ◽  
Lijia Lv ◽  
Jing Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Breast Cancer Stem Cells ◽  
Cancer Proliferation ◽  
Mammosphere Formation

Abstract Purpose: TFEB is a key regulator of autophagy-lysosomal biogenesis pathways, while its dysregulation is highly prevalent in various human cancers, but the specific contribution to breast cancer remains poorly understood. The main purpose of this study is to explore the role of TFEB in breast cancer proliferation, metastasis and maintaining breast cancer stem cells (BCSCs) traits, thus uncovering its underlying mechanism.Methods: Bioinformatics, western blotting and immunohistochemical staining were applied to analyze the expression of TFEB in breast cancer. Stable down-regulation TFEB cells were established in MCF-7 and MDA-MB-231 breast cancer cell lines. MTT, clone formation, wound healing, transwell and 3D tumor invasion assays were used to evaluate the proliferation, migration and invasion ability of breast cancer cells. Mammosphere formation, immunocytochemical (ICC) staining were used to detect the effect of down-regulating TFEB on breast cancer stem cells. Results: we demonstrated that higher expression of TFEB was found in breast cancer. TFEB depletion had inhibitory effects on cellular proliferation, migration and invasion of breast cancer cells. Moreover, knockdown TFEB decreased mammosphere formation ability of BCSCs and expression of cancer stem cell markers. Autophagy-lysosomal related proteins were decreased by down regulation of TFEB. Conclusion: we uncovered a critical role of TFEB in breast cancer proliferation and metastasis, and BCSCs self-renewal and stemness. The underlying mechanisms involve in maintaining BCSCs traits, and dysregulating lysosome functions.

scholarly journals Rho GTPases: Big Players in Breast Cancer Initiation, Metastasis and Therapeutic Responses

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2167
Author(s):  
Brock Humphries ◽  
Zhishan Wang ◽  
Chengfeng Yang
Keyword(s):  
Breast Cancer ◽  
Membrane Trafficking ◽  
Rho Gtpases ◽  
Migration And Invasion ◽  
Breast Cancer Patients ◽  
Cancer Initiation ◽  
Cell Type Specific ◽  
And Function ◽  
Therapeutic Responses

Rho GTPases, a family of the Ras GTPase superfamily, are key regulators of the actin cytoskeleton. They were originally thought to primarily affect cell migration and invasion; however, recent advances in our understanding of the biology and function of Rho GTPases have demonstrated their diverse roles within the cell, including membrane trafficking, gene transcription, migration, invasion, adhesion, survival and growth. As these processes are critically involved in cancer initiation, metastasis and therapeutic responses, it is not surprising that studies have demonstrated important roles of Rho GTPases in cancer. Although the majority of data indicates an oncogenic role of Rho GTPases, tumor suppressor functions of Rho GTPases have also been revealed, suggesting a context and cell-type specific function for Rho GTPases in cancer. This review aims to summarize recent progresses in our understanding of the regulation and functions of Rho GTPases, specifically in the context of breast cancer. The potential of Rho GTPases as therapeutic targets and prognostic tools for breast cancer patients are also discussed.

Role of extracellular matrix in regulation of staurosporine-induced apoptosis in breast cancer cells

2005 ◽  
Author(s):  
F. Vasaturo ◽  
C. Malacrino ◽  
E. Sallusti ◽  
G. Coppotelli ◽  
P. Birarelli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Induced Apoptosis
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