TWIST1 promotes invasion through mesenchymal change in human glioblastoma

Mikheeva, Svetlana A.; Mikheev, Andrei M.; Petit, Arnaud; Beyer, Richard P.; Oxford, Robert G.; Khorasani, Leila; Maxwell, John P.; Glackin, Carlotta A.; Wakimoto, Hiroaki; González-Herrero, Inés; Sánchez-Garcı́a, Isidro; Silber, John R.; Horner, Philip J.; Rostomily, Robert

doi:10.1186/1476-4598-9-194

Cited by 253 publications

(236 citation statements)

References 55 publications

(66 reference statements)

Supporting

Mentioning

222

Contrasting

Order By: Relevance

“…In contrast, knockdown of POSTN, TWIST, or TGFB1I1 transcript suppressed the wound migration of RA-FLSs stimulated with culture medium containing 10% (vol/vol) FBS (Fig. 4D), which is consistent with earlier reports showing that POSTN and TWIST1 promote migration and invasion of several types of cancer cells (19)(20)(21). The IL-1β-induced FLS migration was also mitigated by either POSTN or TWIST1 siRNA, but it was not affected by TGFB1I1 siRNA (Fig.…”

Section: Selection Of Potential Regulators For Fls Migration and Invasupporting

confidence: 82%

“…Among the four modules related to the invasive potential of RAFLSs in the above network model, regulation of EMT has been most closely associated with the invasion of cancer, including breast cancer, glioblastoma, and esophageal cancer (19)(20)(21). Interestingly, in our network model, 5 of 13 candidates (TWIST1, POSTN, TFGB1I1, TRIM28, and SMAD7) were involved in regulation of EMT (Fig.…”

Section: Selection Of Potential Regulators For Fls Migration and Invamentioning

confidence: 99%

See 1 more Smart Citation

Identification of key regulators for the migration and invasion of rheumatoid synoviocytes through a systems approach

You

Yoo²,

Choi³

et al. 2013

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

View full text Add to dashboard Cite

Rheumatoid synoviocytes, which consist of fibroblast-like synoviocytes (FLSs) and synovial macrophages (SMs), are crucial for the progression of rheumatoid arthritis (RA). Particularly, FLSs of RA patients (RA-FLSs) exhibit invasive characteristics reminiscent of cancer cells, destroying cartilage and bone. RA-FLSs and SMs originate differently from mesenchymal and myeloid cells, respectively, but share many pathologic functions. However, the molecular signatures and biological networks representing the distinct and shared features of the two cell types are unknown. We performed global transcriptome profiling of FLSs and SMs obtained from RA and osteoarthritis patients. By comparing the transcriptomes, we identified distinct molecular signatures and cellular processes defining invasiveness of RA-FLSs and proinflammatory properties of RA-SMs, respectively. Interestingly, under the interleukin-1β (IL-1β)–stimulated condition, the RA-FLSs newly acquired proinflammatory signature dominant in RA-SMs without losing invasive properties. We next reconstructed a network model that delineates the shared, RA-FLS–dominant (invasive), and RA-SM–dominant (inflammatory) processes. From the network model, we selected 13 genes, including periostin, osteoblast-specific factor (POSTN) and twist basic helix–loop–helix transcription factor 1 (TWIST1), as key regulator candidates responsible for FLS invasiveness. Of note, POSTN and TWIST1 expressions were elevated in independent RA-FLSs and further instigated by IL-1β. Functional assays demonstrated the requirement of POSTN and TWIST1 for migration and invasion of RA-FLSs stimulated with IL-1β. Together, our systems approach to rheumatoid synovitis provides a basis for identifying key regulators responsible for pathological features of RA-FLSs and -SMs, demonstrating how a certain type of cells acquires functional redundancy under chronic inflammatory conditions.

show abstract

Section: Selection Of Potential Regulators For Fls Migration and Invasupporting

confidence: 82%

Section: Selection Of Potential Regulators For Fls Migration and Invamentioning

confidence: 99%

Identification of key regulators for the migration and invasion of rheumatoid synoviocytes through a systems approach

You

Yoo²,

Choi³

et al. 2013

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

View full text Add to dashboard Cite

show abstract

“…These findings are consistent with the importance of loss of cellular polarity and cell-cell adhesion, deregulated cytoskeletal dynamics, and enhanced cell motility in cancer, and represent a prominent phenotype typified by the epithelial-mesenchymal transition (EMT) phenomenon (41,42). EMT-like cytoskeletal configuration changes have also been documented in diverse solid tumors including GBM (43,44). Our study shows that loss of the Myt1L-A2BP1 axis can promote a gliomagenesis-prone cytoskeletal state through modulating alternative splicing of multiple cytoskeleton regulators including actin regulator TPM1.…”

Section: Discussionsupporting

confidence: 68%

Neutralization of terminal differentiation in gliomagenesis

Yuan

et al. 2013

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

View full text Add to dashboard Cite

An immature state of cellular differentiation-characterized by stem cell-like tendencies and impaired differentiation-is a hallmark of cancer. Using glioblastoma multiforme (GBM) as a model system, we sought to determine whether molecular determinants that drive cells toward terminal differentiation are also genetically targeted in carcinogenesis and whether neutralizing such genes also plays an active role to reinforce the impaired differentiation state and promote malignancy. To that end, we screened 71 genes with known roles in promoting nervous system development that also sustain copy number loss in GBM through antineoplastic assay and identified A2BP1 (ataxin 2 binding protein 1, Rbfox1), an RNAbinding and splicing regulator that is deleted in 10% of GBM cases. Integrated in silico analysis of GBM profiles to elucidate the A2BP1 pathway and its role in glioma identified myelin transcription factor 1-like (Myt1L) as a direct transcriptional regulator of A2BP1. Reintroduction of A2BP1 or Myt1L in GBM cell lines and glioma stem cells profoundly inhibited tumorigenesis in multiple assays, and conversely, shRNA-mediated knockdown of A2BP1 or Myt1L in premalignant neural stem cells compromised neuronal lineage differentiation and promoted orthotopic tumor formation. On the mechanistic level, with the top-represented downstream target TPM1 as an illustrative example, we demonstrated that, among its multiple functions, A2BP1 serves to regulate TPM1's alternative splicing to promote cytoskeletal organization and terminal differentiation and suppress malignancy. Thus, in addition to the activation of self-renewal pathways, the neutralization of genetic programs that drive cells toward terminal differentiation may also promote immature and highly plastic developmental states that contribute to the aggressive malignant properties of GBM.oncogenomics | cancer stem cells

show abstract

“…Rapid tumor progression and diffuse invasion of brain tissue restrict the therapeutic options and result in poor prognosis despite advances in the understanding of this tumor's molecular biology and pathophysiology [1][2][3][4]. Current standard therapy consists of a combination of tumor resection, irradiation and temozolomide.…”

Section: Introductionmentioning

confidence: 99%

“…This fact encouraged extensive investigations studying the molecular mechanisms underlying GBM resistance to EGFR-targeted therapy. Epithelial to mesenchymal transition (EMT) is considered an important factor contributing to resistance towards this therapy by diminishing the molecular target [1][2][3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%