Actin Cytoskeleton in Cancer Progression and Metastasis - Part B

Mechanical microenvironments, such as extracellular matrix stiffness and strain, have crucial roles in cancer progression. Cells sense their microenvironments with mechanosensing biomolecules, which is accompanied by the modulation of actin cytoskeleton structures, and the signals are subsequently transduced downstream as biochemical signals. The tumor suppressors p53 and retinoblastoma protein (Rb) are known to prevent cancer progression. The p53 and Rb signaling pathways are disrupted in many types of cancers. Here, we review recent findings about the roles of these tumor suppressors in the regulation of mechanosensing biomolecules and the actin cytoskeleton. We further discuss how dysfunction in the p53- and/or Rb-mediated mechanosignaling pathways is potentially involved in cancer progression. These pathways might provide good targets for developing anticancer therapies.

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Ubiquitination and Long Non-coding RNAs Regulate Actin Cytoskeleton Regulators in Cancer Progression

International Journal of Molecular Sciences ◽

10.3390/ijms20122997 ◽

2019 ◽

Vol 20 (12) ◽

pp. 2997 ◽

Cited By ~ 3

Author(s):

Xuda Ma ◽

Yamei Dang ◽

Xiaowen Shao ◽

Xuechun Chen ◽

Fei Wu ◽

...

Keyword(s):

Actin Cytoskeleton ◽

Cancer Progression ◽

Rho Gtpases ◽

Actin Filaments ◽

Cancer Metastasis ◽

Coiled Coil ◽

Lim Domain ◽

E3 Ligases ◽

Protein Levels ◽

Family Protein

Actin filaments are a major component of the cytoskeleton in eukaryotic cells and play an important role in cancer metastasis. Dynamics and reorganization of actin filaments are regulated by numerous regulators, including Rho GTPases, PAKs (p21-activated kinases), ROCKs (Rho-associated coiled-coil containing kinases), LIMKs (LIM domain kinases), and SSH1 (slingshot family protein phosphate 1). Ubiquitination, as a ubiquitous post-transcriptional modification, deceases protein levels of actin cytoskeleton regulatory factors and thereby modulates the actin cytoskeleton. There is increasing evidence showing cytoskeleton regulation by long noncoding RNAs (lncRNAs) in cancer metastasis. However, which E3 ligases are activated for the ubiquitination of actin-cytoskeleton regulators involved in tumor metastasis remains to be fully elucidated. Moreover, it is not clear how lncRNAs influence the expression of actin cytoskeleton regulators. Here, we summarize physiological and pathological mechanisms of lncRNAs and ubiquitination control mediators of actin cytoskeleton regulators which that are involved in tumorigenesis and tumor progression. Finally, we briefly discuss crosstalk between ubiquitination and lncRNA control mediators of actin-cytoskeleton regulators in cancer.

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1093 LIVER CANCER PROGRESSION FROM DYSPLASIA TO NEOPLASIA REVEALED BY TRANSCRIPTOME ANALYSIS: REARRANGEMENT OF ACTIN CYTOSKELETON AS AN EARLY EVENT

Journal of Hepatology ◽

10.1016/s0168-8278(13)61094-6 ◽

2013 ◽

Vol 58 ◽

pp. S447

Author(s):

J.E. Torres-Mena ◽

R. Sánchez-Rodríguez ◽

L. del Pozo-Yauner ◽

S. Villa-Treviño ◽

J.I. Pérez-Carreón

Keyword(s):

Liver Cancer ◽

Actin Cytoskeleton ◽

Cancer Progression ◽

Transcriptome Analysis ◽

Early Event

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Actin Cytoskeleton in Cancer Progression and Metastasis - Part A

10.1016/s1937-6448(20)x0007-4 ◽

2020 ◽

Keyword(s):

Actin Cytoskeleton ◽

Cancer Progression

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scribble abrogation induces tumor growth through JNK-Wnt pathways depending on cellular-microenvironment in Drosophila wing imaginal tissue

10.1101/721407 ◽

2019 ◽

Author(s):

Amarish Kumar Yadav ◽

Roshan Fatima ◽

Saripella Srikrishna

Keyword(s):

Tumor Growth ◽

Actin Cytoskeleton ◽

Tumor Progression ◽

Cell Polarity ◽

Cancer Progression ◽

Wing Disc ◽

Cellular Microenvironment ◽

Large Area ◽

Wnt Pathways ◽

Cytoskeleton Disruption

Abstractscribble (scrib) is a cell-polarity determinant in Drosophila and human. Cell polarity plays a crucial role in the maintenance of tissue homeostasis and its disruption leads to neoplastic cancer progression. However, the underlying mechanisms by which loss of cell-polarity regulators drives cancer progression are poorly known. In this study, we have explored the tumor progression mechanisms upon scrib knockdown in Drosophila wing imaginal disc using UASRNAi-GAL4 approach. We have found that scrib knockdown in wing disc leads to tumor growth with disrupted actin cytoskeleton, loss of cell-polarity and elevated JNK signalling, resulting in absolute early pupal lethality. Further, scrib abrogated cells in a large area of the disc are capable of invading the surrounding wild type cells and inducing apoptosis along with compensatory proliferation through JNK-Wnt pathways. Moreover, JNK pathway upstream candidate hep (JNKK) knockdown in scrib abrogated cells rescues the cell polarity defects, actin cytoskeleton disruption and tumor growth, while constitutive hep activation further aggravates the tumor phenotype. Interestingly, generation of undead cells by apoptosis inhibition in these hep knockdown cells by p35 expression further leads to tumor development. Hence, we conclude that scrib knockdown in a large area of wing disc might have a ‘group-protection’ and ‘undead-cells’ microenvironment that modulates the action of JNK signalling resulting in tumor formation. Furthermore, JNK dependent activation of Wnt/Ca2+ signalling also supports the tumor growth and actin cytoskeleton disruption. Thus, our results importantly highlight the role of JNK signalling in tumor progression upon scrib loss of function depending on cellular-microenvironment.

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Alterations of the apical junctional complex and actin cytoskeleton and their role in colorectal cancer progression

Tissue Barriers ◽

10.1080/21688370.2015.1017688 ◽

2015 ◽

Vol 3 (3) ◽

pp. e1017688 ◽

Cited By ~ 11

Author(s):

Adriana Sartorio Gehren ◽

Murilo Ramos Rocha ◽

Waldemir Fernandes de Souza ◽

José Andrés Morgado-Díaz

Keyword(s):

Colorectal Cancer ◽

Actin Cytoskeleton ◽

Cancer Progression ◽

Junctional Complex ◽

Apical Junctional Complex ◽

Colorectal Cancer Progression

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MaTAR25 LncRNA Regulates the Tensin1 Gene to Impact Breast Cancer Progression

10.1101/2020.02.03.931881 ◽

2020 ◽

Cited By ~ 1

Author(s):

Kung-Chi Chang ◽

Sarah D. Diermeier ◽

Allen T. Yu ◽

Lily D. Brine ◽

Suzanne Russo ◽

...

Keyword(s):

Breast Cancer ◽

Actin Cytoskeleton ◽

Cancer Progression ◽

Cancer Metastasis ◽

Focal Adhesions ◽

Breast Cancer Progression ◽

Migration And Invasion ◽

Mammary Tumor Cell ◽

Human Ortholog

SUMMARYMisregulation of long non-coding RNA genes has been linked to a wide variety of cancer types. Here we report on Mammary Tumor Associated RNA 25 (MaTAR25), a nuclear enriched and chromatin associated lncRNA that plays a role in mammary tumor cell proliferation, migration, and invasion, both in vitro and in vivo. MaTAR25 functions by interacting with purine rich element binding protein B (PURB), and associating with a major downstream target gene Tensin 1 (Tns1) to regulate its expression in trans. Knockout of MaTAR25 results in down-regulation of Tns1 leading to a reorganization of the actin cytoskeleton, and a reduction of focal adhesions and microvilli. The human ortholog of MaTAR25, LINC01271, is upregulated with human breast cancer stage and metastasis.SIGNIFICANCELncRNAs have great potential to reveal new regulatory mechanisms of function as well as having exciting therapeutic capacity given their ease of being targeted by nucleic acid drugs. Our study of MaTAR25, and its human ortholog LINC01271, reveal an unexpected function of this lncRNA in breast cancer progression by regulating Tns1 gene expression, whose protein product is a critical component of focal adhesions linking signaling between the extracellular matrix and the actin cytoskeleton. We identified LINC01271 as the human ortholog of MaTAR25, and importantly, increased expression of LINC01271 is associated with poor patient prognosis and cancer metastasis. Our findings demonstrate that LINC01271 represents an exciting therapeutic target to alter breast cancer progression.

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MaTAR25 lncRNA regulates the Tensin1 gene to impact breast cancer progression

Nature Communications ◽

10.1038/s41467-020-20207-y ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Kung-Chi Chang ◽

Sarah D. Diermeier ◽

Allen T. Yu ◽

Lily D. Brine ◽

Suzanne Russo ◽

...

Keyword(s):

Breast Cancer ◽

Actin Cytoskeleton ◽

Cancer Progression ◽

Mammary Tumor ◽

Focal Adhesions ◽

Breast Cancer Progression ◽

Migration And Invasion ◽

Mammary Tumor Cell

AbstractMisregulation of long non-coding RNA (lncRNA) genes has been linked to a wide variety of cancer types. Here we report on Mammary Tumor Associated RNA 25 (MaTAR25), a nuclear enriched and chromatin associated lncRNA that plays a role in mammary tumor cell proliferation, migration, and invasion, both in vitro and in vivo. MaTAR25 functions by interacting with purine rich element binding protein B (PURB), and associating with a major downstream target gene Tensin1 (Tns1) to regulate its expression in trans. The Tns1 protein product is a critical component of focal adhesions linking signaling between the extracellular matrix and the actin cytoskeleton. Knockout of MaTAR25 results in down-regulation of Tns1 leading to a reorganization of the actin cytoskeleton, and a reduction of focal adhesions and microvilli. We identify LINC01271 as the human ortholog of MaTAR25, and importantly, increased expression of LINC01271 is associated with poor patient prognosis and metastasis. Our findings demonstrate that LINC01271 represents a potential therapeutic target to alter breast cancer progression.

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