MIEN1 promotes oral cancer progression and implicates poor overall survival

Rajendiran, Smrithi; Kpetemey, Marilyne; Maji, Sayantan; Gibbs, Lee D.; Dasgupta, Subhamoy; Mantsch, Rebecca; Hare, Richard J.; Vishwanatha, Jamboor K.

doi:10.1080/15384047.2015.1040962

Cited by 20 publications

(16 citation statements)

References 44 publications

(53 reference statements)

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“…In breast tumors, FAK mediates tumor cell adhesion, and its overexpression induces survival signals to promote breast cancer growth and metastasis [42, 50, 51]. Furthermore, our results demonstrate that depletion of MIEN1 leads to a reduction in FAK phosphorylation at Tyr-925 along with reduced phosphorylation of previously shown markers of motility such as Akt, Erk1/2 and NF- κB [14, 18, 19, 43, 52]. These results are consistent with previous findings which demonstrate that Src-mediated phosphorylation of FAK at Tyr-925 creates a binding site for Grb2 and then stimulate mitogen-activated protein kinase (MAPK) signaling via a FAK/Grb2/Sos/Ras/Erk2 pathway [43, 52].…”

Section: Discussionmentioning

confidence: 63%

MIEN1 drives breast tumor cell migration by regulating cytoskeletal-focal adhesion dynamics

et al. 2016

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Migration and invasion enhancer 1 (MIEN1) is an important regulator of cell migration and invasion. MIEN1 overexpression represents an oncogenic event that promotes tumor cell dissemination and metastasis. The underlying mechanism by which MIEN1 regulates migration and invasion has yet to be deciphered. Here, we demonstrate that MIEN1 acts as a cytoskeletal-signaling adapter protein to drive breast cancer cell migration. MIEN1 localization is concentrated underneath the actin-enriched protrusive structures of the migrating breast cancer cells. Depletion of MIEN1 led to the loss of actin-protrusive structures whereas the over-expression of MIEN1 resulted in rich and thick membrane extensions. Knockdown of MIEN1 also decreased the cell-substratum adhesion, suggesting a role for MIEN1 in actin cytoskeletal dynamics. Our results show that MIEN1 supports the transition of G-actin to F-actin polymerization and stabilizes F-actin polymers. Additionally, MIEN1 promotes cellular adhesion and actin dynamics by inducing phosphorylation of FAK at Tyr-925 and reducing phosphorylation of cofilin at Ser-3, which results in breast cancer cell migration. Collectively, our data show that MIEN1 plays an essential role in maintaining the plasticity of the dynamic membrane-associated actin cytoskeleton, which leads to an increase in cell motility. Hence, targeting MIEN1 might represent a promising means to prevent breast tumor metastasis.

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Section: Discussionmentioning

confidence: 63%

MIEN1 drives breast tumor cell migration by regulating cytoskeletal-focal adhesion dynamics

et al. 2016

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“…The paranuclear staining of cancer markers have previously been correlated with tumor progression and shortened patient survival. 20 It is currently unknown what is the significance for IL-5Ra paranuclear staining as it was not associated with the expression of IL-5Ra. In addition, in primary invasive bladder tumors, the tumor cells were nearly all positive for IL-5Ra ( Figs.…”

Section: Discussionmentioning

confidence: 99%

Targeting IL-5Rα with antibody-conjugates reveals a strategy for imaging and therapy for invasive bladder cancer

Paquette

Vilera-Perez²,

Beaudoin

et al. 2017

OncoImmunology

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Despite the high interest and concern due to an increasing incidence and death rate, patients who develop muscle invasive bladder cancer (MIBC) have few options available. However, the past decade has produced many candidate bladder tumor-specific markers but further development of these markers is still needed for creating effective targeted medications to solve this urgent need. Interleukin-5 receptor α-subunit (IL-5Rα) has recently been reported to be involved in MIBC progression. Thus, we aimed to validate IL-5Rα as a target for antibody-conjugates to better manage patients with MIBC. Patients were recruited and their tumors were processed for IL-5Rα immunohistochemical analysis. NOD/SCID mice were also heterotopically implanted with the human MIBC HT-1376 and HT-B9 cell lines and established xenografts immunohistochemically evaluated for IL-5Rα and compared against patient tumors. Using the mAb A14, an antibody-drug conjugate (ADC) and a radiolabeled immunoconjugate (RIC) were developed by conjugating to vinblastine and to the positron emitter copper-64 (Cu), respectively. As a proof-of-concept for ADC and RIC efficacy, cytotoxicity and positron emission tomography (PET) imaging in tumor-bearing mice were performed, respectively. In addition, as rapid internalization and accumulation are important components for effective antibody-conjugates, we evaluated these aspects in response to IL-5 and Cu-A14 treatments. Our findings suggest that although IL-5Rα protein expression is preferentially increased in MIBC, it is rapid IL-5Rα-mediated internalization allowing vinblastine-A14 to have cytotoxic activity andCu-A14 to detect MIBC tumors . This is the first report to elucidate the potential of IL-5Rα as an attractive MIBC target for antibody-conjugate applications.

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“…Taken together, our data imply that other mechanisms are involved in the regulation of cell proliferation by GRB7 , MIEN1 , or PGAP3 . To the best of our knowledge, the present study is the first to report the functional role of these genes in GC cells, although a few studies have reported the cancer-promoting role of MIEN1 in breast [ 32 ], oral [ 33 ], and prostate cancer [ 34 ], and the involvement of GRB7 or STARD3 in breast cancer cell invasion, survival [ 35 ], and cell proliferation [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Genes co-amplified with ERBB2 or MET as novel potential cancer-promoting genes in gastric cancer

Kwon

Kim

Song³

et al. 2017

Oncotarget

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Gastric cancer (GC), one of the most common cancers worldwide, has a high mortality rate due to limited treatment options. Identifying novel and promising molecular targets is a major challenge that must be overcome if treatment of advanced GC is to be successful. Here, we used comparative genomic hybridization and gene expression microarrays to examine genome-wide DNA copy number alterations (CNAs) and global gene expression in 38 GC samples from old and young patients. We identified frequent CNAs, which included copy number gains on chromosomes 3q, 7p, 8q, 20p, and 20q and copy number losses on chromosomes 19p and 21p. The most frequently gained region was 7p21.1 (55%), whereas the most frequently deleted region was 21p11.1 (50%). Recurrent highly amplified regions 17q12 and 7q31.1-7q31.31 harbored two well-known oncogenes: ERBB2 and MET. Correlation analysis of CNAs and gene expression levels identified CAPZA2 (co-amplified with MET) and genes GRB7, MIEN1, PGAP3, and STARD3 (co-amplified with ERBB2) as potential candidate cancer-promoting genes (CPGs). Public dataset analysis confirmed co-amplification of these genes with MET or ERBB2 in GC tissue samples, and revealed that high expression (except for PGAP3) was significantly associated with shorter overall survival. Knockdown of these genes using small interfering RNA led to significant suppression of GC cell proliferation and migration. Reduced GC cell proliferation mediated by CAPZA2 knockdown was attributable to attenuated cell cycle progression and increased apoptosis. This study identified novel candidate CPGs co-amplified with MET or ERBB2, and suggests that they play a functional role in GC.

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MIEN1 promotes oral cancer progression and implicates poor overall survival

Cited by 20 publications

References 44 publications

MIEN1 drives breast tumor cell migration by regulating cytoskeletal-focal adhesion dynamics

MIEN1 drives breast tumor cell migration by regulating cytoskeletal-focal adhesion dynamics

Targeting IL-5Rα with antibody-conjugates reveals a strategy for imaging and therapy for invasive bladder cancer

Genes co-amplified with ERBB2 or MET as novel potential cancer-promoting genes in gastric cancer

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