Filamin A regulates focal adhesion disassembly and suppresses breast cancer cell migration and invasion

Xu, Yingjie; Bismar, Tarek A.; Shi, Jie; Xu, Bin; Kristiansen, Glen; Varga, Zsuzsanna; Teng, Lianghong; Ingber, Donald E.; Mammoto, Akiko; Kumar, Rakesh; Alaoui‐Jamali, Moulay A.

doi:10.1083/jcb1912oia5

Cited by 34 publications

(50 citation statements)

References 30 publications

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“…The role of FLNA in tumor invasiveness and metastases suggested by in vitro cell motility studies is currently under scrutiny (10,22,(31)(32)(33). However, other roles for FLNA in cancer have been proposed.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-induced and calpain-dependent cleavage of filamin A regulates the hypoxic response

Zheng¹,

Zhou

Rouhi

et al. 2014

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

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The cellular response to hypoxia is regulated by hypoxia-inducible factor-1α and -2α (HIF-1α and -2α). We have discovered that filamin A (FLNA), a large cytoskeletal actin-binding protein, physically interacts with HIF-1α and promotes tumor growth and angiogenesis. Hypoxia induces a calpain-dependent cleavage of FLNA to generate a naturally occurring C-terminal fragment that accumulates in the cell nucleus. This fragment interacts with the N-terminal portion of HIF-1α spanning amino acid residues 1-390 but not with HIF-2α. In hypoxia this fragment facilitates the nuclear localization of HIF-1α, is recruited to HIF-1α target gene promoters, and enhances HIF-1α function, resulting in up-regulation of HIF-1α target gene expression in a hypoxia-dependent fashion. These results unravel an important mechanism that selectively regulates the nuclear accumulation and function of HIF-1α and potentiates angiogenesis and tumor progression.cancer | subcellular localization | signal transduction

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Section: Discussionmentioning

confidence: 99%

Hypoxia-induced and calpain-dependent cleavage of filamin A regulates the hypoxic response

Zheng¹,

Zhou

Rouhi

et al. 2014

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

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“…42,86 Consistent with this notion, diminished expression of FLNa increases the invasiveness of human breast cancer cells. 87 Since FLNa silencing also induces activation of calpain, which leads to degradation of focal adhesion proteins, 88,89 suppression of FLNa expression may facilitate focal adhesion turnover, thereby promoting the invasion. Recycling of integrin is also essential for sustained cell migration.…”

Section: Role Of Filamin In Integrin-dependent Cell Adhesion and Migrmentioning

confidence: 99%

The filamins

Nakamura

Stossel²,

Hartwig³

2011

Cell Adhesion & Migration

408

244

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“…25 Blots were detected using the antibodies for anti-E-cadherin (1:1000 dilution; Cell Signaling Technology, Inc., Beverly, Mass), anti-Twist1 (1:500 dilution; Abnova), anti-b-catenin (1:1000 dilution; Abcam plc., Cambridge, United Kingdom), and anti-GAPDH (1:10,000 dilution; Cedarlane, Burlington, Ontario, Canada), and signals were detected with peroxidaseconjugated secondary antibodies and an enhanced chemiluminescence detection system.…”

Section: Western Blot Analysismentioning

confidence: 99%

TWIST1 is a molecular marker for a poor prognosis in oral cancer and represents a potential therapeutic target

Silva

Alaoui‐Jamali

Soares

et al. 2013

Cancer

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BACKGROUND: Locoregional recurrence and distant metastases are ominous events in patients with advanced oral squamous cell carcinoma (OSCC). The objective of this study was to identify functional biomarkers that are predictive of OSCC progression to metastasis. METHODS: The expression profile of a network of epithelial-mesenchymal transition (EMT) genes was investigated in a large cohort of patients with progressive OSCC using a complimentary DNA microarray platform coupled to quantitative reverse transcriptase-polymerase chain reaction and immunohistochemical analyses. Therapeutic potential was investigated in vitro and in vivo using an orthotopic mouse model of metastatic OSCC growing in the tongue microenvironment. RESULTS: Among deregulated EMT genes, the Twist-related protein 1 (TWIST1) transcription factor and several of its regulated genes were significantly overexpressed across advanced stages of OSCC. This result was corroborated by the clinical observation that Twist1 up-regulation predicted the occurrence of lymph node and lung metastases as well as poor patient survival. In support of Twist1 as a driver of OSCC progression, the up-regulation of Twist1 was observed in cells isolated from patients with metastatic OSCC. The inhibition of Twist1 in these metastatic cells induced a potent inhibition of cell invasiveness in vitro as well as progression in vivo. CONCLUSIONS: The current results provide evidence for the prognostic value and therapeutic potential of a network of Twist genes in patients with advanced OSCC. Cancer 2014;120:352-62.

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Filamin A regulates focal adhesion disassembly and suppresses breast cancer cell migration and invasion

Cited by 34 publications

References 30 publications

Hypoxia-induced and calpain-dependent cleavage of filamin A regulates the hypoxic response

Hypoxia-induced and calpain-dependent cleavage of filamin A regulates the hypoxic response

The filamins

TWIST1 is a molecular marker for a poor prognosis in oral cancer and represents a potential therapeutic target

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