EPLIN: a fundamental actin regulator in cancer metastasis?

Collins, Ross J.; Jiang, Wen Guo; Hargest, Rachel; Mason, Malcolm David; Sanders, Andrew

doi:10.1007/s10555-015-9595-8

Cited by 42 publications

(56 citation statements)

References 45 publications

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“…Previous studies evaluating EPLIN in cancer progression have identified loss of EPLIN in aggressive cancer and suggest a regulatory role for EPLIN as a tumor suppressor . Additionally, several mechanisms have been reported for the regulation of EPLIN expression, including ERK, EGF, DNp73 and p53, and provide important insight into how EPLIN may be regulated at a functional or expressional level.…”

Section: Discussionmentioning

confidence: 93%

“…Prostate cancer is the second most common cancer in the UK and accounts for >11,000 cancer‐related deaths . Epithelial protein lost in neoplasm (EPLIN) is a molecule that is frequently lost in cancer and has been implicated in the initiation of epithelial–mesenchymal transition, in addition to having tumor suppressive roles in cancer progression and development …”

Section: Introductionmentioning

confidence: 99%

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Mechanistic insights of epithelial protein lost in neoplasm in prostate cancer metastasis

Collins

Morgan

Owen

et al. 2018

Intl Journal of Cancer

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EPLIN is frequently downregulated or lost in various cancers. The purpose of this study was to evaluate the importance of EPLIN in prostate cancer progression, with particular focus on the mechanistic implications to elucidate EPLIN's tumor suppressive function in cancer. EPLIN expression was evaluated in prostate cancer cell lines and tissues. PC-3 and LNCaP EPLINα overexpression models were generated through transfection with EPLINα sequence and EPLIN knockdown was achieved using shRNA in CA-HPV-10 cells. Functional assays were performed to evaluate cellular characteristics and potential mechanisms were evaluated using a protein microarray, and validated using western blot analysis. EPLIN expression was reduced in clinical prostate cancer sections, including hyperplasia (p ≤ 0.001) and adenocarcinoma (p = 0.005), when compared to normal prostate tissue. EPLINα overexpression reduced cell growth, migration and invasion, and influenced transcript, protein and phosphoprotein expression of paxillin, FAK and Src. EPLIN knockdown increased the invasive and migratory nature of CA-HPV-10 cells and also induced changes to FAK and Src total and/or phospho expression. Functional characterization of cellular migration and invasion in addition to FAK and Src inhibition demonstrated differential effects between control and EPLINα overexpression and EPLIN knockdown cell lines. This study highlights that EPLIN expression in prostate cancer is able to influence several aspects of cancer cell characteristics, including cell growth, migration and invasion. The mechanism of the tumor suppressive action of EPLIN remains to be fully elucidated; and this study proposes a role for EPLIN's ability to regulate the aggressive characteristics of prostate cancer cells partially through regulating FAK/Src signaling.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Mechanistic insights of epithelial protein lost in neoplasm in prostate cancer metastasis

Collins

Morgan

Owen

et al. 2018

Intl Journal of Cancer

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“…Importantly, a reduction of hCDC14A and eplin levels is frequently observed in colorectal carcinoma and is associated with poor prognosis in cancer patients (Fig. 5 I and J) (20,34,35). Collectively, we propose that the balance of eplin phosphorylation that is maintained by the antagonistic activities of ERK and hCDC14A toward conserved phosphorylation sites on eplin plays a key role in regulating actin dynamics to modulate cell migration and adhesion of both normal and transformed cells (Fig.…”

Section: Discussionmentioning

confidence: 69%

“…Downregulation of eplin frequently occurs in cancer tissues and contributes to the epithelia-to-mesenchymal transition (EMT) that enhances cancer cell metastasis and chemo-resistance of tumors (23,(33)(34)(35)(36)(37).…”

Section: Phosphomentioning

confidence: 99%

Human phosphatase CDC14A regulates actin organization through dephosphorylation of epithelial protein lost in neoplasm

Chen

Uddin

Hardt

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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CDC14 is an essential dual-specificity phosphatase that counteracts CDK1 activity during anaphase to promote mitotic exit in Saccharomyces cerevisiae. Surprisingly, human CDC14A is not essential for cell cycle progression. Instead, it regulates cell migration and cell adhesion. Little is known about the substrates of hCDC14A and the counteracting kinases. Here, we combine phospho-proteome profiling and proximity-dependent biotin identification to identify hCDC14A substrates. Among these targets were actin regulators, including the tumor suppressor eplin. hCDC14A counteracts EGF-induced rearrangements of actin cytoskeleton by dephosphorylating eplin at two known extracellular signal-regulated kinase sites, serine 362 and 604. hCDC14A(PD) and eplin knockout cell lines exhibited down-regulation of E-cadherin and a reduction in alpha/beta-catenin at cell-cell adhesions. Reduction in the levels of hCDC14A and eplin mRNA is frequently associated with colorectal carcinoma and is correlated with poor prognosis. We therefore propose that eplin dephosphorylation by hCDC14A reduces actin dynamics to restrict tumor malignancy

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“…quite recently showed that doliculide treatment of p53 wild‐type cancer cells alters up to 13% of senescence‐related genes at nontoxic concentrations. Like tubulin, actin is also implicated in the metastatic process …”

Section: Mollusk‐derived Anticancer Agentsmentioning

confidence: 99%

Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance

Ciavatta

Lefranc

Carbone

et al. 2016

Medicinal Research Reviews

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The chemical investigation of marine mollusks has led to the isolation of a wide variety of bioactive metabolites, which evolved in marine organisms as favorable adaptations to survive in different environments. Most of them are derived from food sources, but they can be also biosynthesized de novo by the mollusks themselves, or produced by symbionts. Consequently, the isolated compounds cannot be strictly considered as “chemotaxonomic markers” for the different molluscan species. However, the chemical investigation of this phylum has provided many compounds of interest as potential anticancer drugs that assume particular importance in the light of the growing literature on cancer biology and chemotherapy. The current review highlights the diversity of chemical structures, mechanisms of action, and, most importantly, the potential of mollusk‐derived metabolites as anticancer agents, including those biosynthesized by mollusks and those of dietary origin. After the discussion of dolastatins and kahalalides, compounds previously studied in clinical trials, the review covers potentially promising anticancer agents, which are grouped based on their structural type and include terpenes, steroids, peptides, polyketides and nitrogen‐containing compounds. The “promise” of a mollusk‐derived natural product as an anticancer agent is evaluated on the basis of its ability to target biological characteristics of cancer cells responsible for poor treatment outcomes. These characteristics include high antiproliferative potency against cancer cells in vitro, preferential inhibition of the proliferation of cancer cells over normal ones, mechanism of action via nonapoptotic signaling pathways, circumvention of multidrug resistance phenotype, and high activity in vivo, among others. The review also includes sections on the targeted delivery of mollusk‐derived anticancer agents and solutions to their procurement in quantity.

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EPLIN: a fundamental actin regulator in cancer metastasis?

Cited by 42 publications

References 45 publications

Mechanistic insights of epithelial protein lost in neoplasm in prostate cancer metastasis

Mechanistic insights of epithelial protein lost in neoplasm in prostate cancer metastasis

Human phosphatase CDC14A regulates actin organization through dephosphorylation of epithelial protein lost in neoplasm

Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance

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