Bit1 in anoikis resistance and tumor metastasis

Jenning, Scott; Pham, Tri; Ireland, Shubha Kale; Ruoslahti, Erkki; Biliran, Hector

doi:10.1016/j.canlet.2013.01.043

Cited by 26 publications

(25 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Malignant tumor cells often develop resistant to anoikis, which enables their survival after detachment from the extracellular matrix. 29, 30, 31, 32 When HeLa cells transfected with Erbin siRNA or control siRNA were cultured in the plates coated with PolyHEMA in the media containing 1% serum or no serum, they grew predominantly as a single-cell suspension and underwent anoikis after loss of detachment for 72 h, with the anoikis rates of 26.83% for the cells in low-serum (1%) media and 30.56% for the cells in serum-free media, respectively (Figures 1a and b). Interestingly, knockdown of Erbin resulted in a significant reduction in anoikis (∼5.75% for low serum and ∼12.79% for serum-free).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Deficiency of Erbin induces resistance of cervical cancer cells to anoikis in a STAT3-dependent manner

Hu¹,

Chen²,

Duan

et al. 2013

Oncogenesis

View full text Add to dashboard Cite

Epithelial cell polarization and integration are essential to their function and loss of epithelial polarity and tissue architecture correlates with the development of aggressive tumors. Erbin is a basolateral membrane-associated protein. The roles of Erbin in establishing cell polarization and regulating cell adhesion have been suggested. Erbin is also a negative regulator in Ras-Raf-ERK (extracellular signal-regulated kinase) signaling pathway. However, the potential functions of Erbin in human cancer are basically unknown. In the present study, we show, for the first time, that loss of Erbin endows cervical cancer cells with resistance to anoikis both in vitro and in vivo and promotes the growth and metastasis of human cervical cancer xenografts in nude mice. We found that knockdown of Erbin induced the phosphorylation, nuclear translocation and transcriptional activities of signal transducer and activator of transcription factor 3 (STAT3) in cervical cancer cells. Overexpression of STAT3C or induction of endogenous STAT3 activation by interleukin (IL)-6 evidently inhibited anoikis of cervical cancer cells, whereas WP1066, a potent inhibitor of Janus-activated kinase 2 (Jak2)/STAT3, effectively blocked the effect of Erbin knockdown on cell survival under anchorage-independent conditions, indicating that loss of Erbin confers resistance of cervical cancer cells to anoikis in a STAT3-dependent manner. Interestingly, IL-6 induced STAT3 activation and Erbin expression simultaneously. Overexpression of STAT3C also significantly upregulated the level of Erbin, whereas the Jak2 inhibitor AG490 remarkably blocked not only STAT3 phosphorylation but also IL-6-induced Erbin expression. Knockdown of Erbin augmented the effects of IL-6 on STAT3 activation and anoikis resistance. In addition, by immunohistochemical analysis of Erbin expression, we demonstrate that the expression of Erbin is significantly decreased or even lost in cervical cancer tissues. These data reveal that Erbin is a novel negative regulator of STAT3, and the IL-6/STAT3/Erbin loop has a crucial role in cervical cancer progression and metastasis.

show abstract

Section: Resultsmentioning

confidence: 99%

“…Anoikis resistance is an important characteristic of tumor cells, 31, 32 enabling tumor cells to invade adjacent tissues and to disseminate to distant organs. The molecular mechanisms of anoikis resistance are mostly unclear.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of Erbin induces resistance of cervical cancer cells to anoikis in a STAT3-dependent manner

Hu¹,

Chen²,

Duan

et al. 2013

Oncogenesis

View full text Add to dashboard Cite

show abstract

“…42 In cancer cells losing the integrin-ECM interaction, the AES/TLE1 heterooligomers are translocated from the nucleus to the cytoplasm following translocation of Bit1 into the cytoplasm. 43 The subsequent downregulation of nuclear TLE1 expression activates the death signaling pathway (Fig. 1).…”

Section: Signaling Death To “Homeless” Cellsmentioning

confidence: 99%

Anoikis and EMT: Lethal "Liaisons" during Cancer Progression

2016

View full text Add to dashboard Cite

Anoikis is a unique mode of apoptotic cell death that occurs consequentially to insufficient cell–matrix interactions. Resistance to anoikis is a critical contributor to tumor invasion and metastasis. The phenomenon is regulated by integrins, which upon engagement with components of the extracellular matrix (ECM) form adhesion complexes and the actin cytoskeleton drives the formation of cell protrusions used to adhere to ECM, directing cell migration. The epithelial-mesenchymal transition (EMT) confers stem cell properties and leads to acquisition of a migratory and invasive phenotype by causing adherens junction breakdown and circumventing anoikis in the tumor microenvironment. The investigation of drug discovery platforms for apoptosis-driven therapeutics identified several novel agents with antitumor action via reversing resistance to anoikis, inhibiting survival pathways and impacting the EMT landscape in human cancer. In this review, we discuss current evidence on the contribution of the anoikis phenomenon functionally linked to EMT to cancer metastasis and the therapeutic value of antitumor drugs that selectively reverse anoikis resistance and/or EMT to impair tumor progression toward the development/optimization of apoptosis-driven therapeutic targeting of metastatic disease.

show abstract

“…However, malignant cells develop resistance to anoikis, leading to increased metastatic potential 41,42 . A seminal mechanistic work on anoikis unraveled its contribution to human cancer metastasis in several different malignancies 43–45 .…”

Section: Discussionmentioning

confidence: 99%

The ZNF304-integrin axis protects against anoikis in cancer

et al. 2015

View full text Add to dashboard Cite

Ovarian cancer is a highly metastatic disease, but no effective strategies to target this metastatic process currently are known. Here, an integrative computational analysis of The Cancer Genome Atlas ovarian cancer dataset coupled with experimental validation identified a novel zinc finger transcription factor ZNF304 as one of the key factors for ovarian cancer metastasis. High tumoral ZNF304 expression was associated with poor overall survival in ovarian cancer patients. Through reverse phase protein array analysis, we demonstrated that ZNF304 promotes multiple proto-oncogenic pathways important for cell survival, migration, and invasion. ZNF304 transcriptionally regulates β1 integrin, which subsequently regulates Src/focal adhesion kinase and paxillin and prevents anoikis. In vivo delivery of ZNF304 siRNA by a novel dual assembly nanoparticle led to sustained gene silencing for 14 days, increased anoikis, and reduced tumor growth in orthotopic mouse models of ovarian cancer. Taken together, ZNF304 is a novel transcriptional regulator of β1 integrin, promotes cancer cell survival, and protects against anoikis in ovarian cancer.

show abstract

Bit1 in anoikis resistance and tumor metastasis

Cited by 26 publications

References 40 publications

Deficiency of Erbin induces resistance of cervical cancer cells to anoikis in a STAT3-dependent manner

Deficiency of Erbin induces resistance of cervical cancer cells to anoikis in a STAT3-dependent manner

Anoikis and EMT: Lethal "Liaisons" during Cancer Progression

The ZNF304-integrin axis protects against anoikis in cancer

Contact Info

Product

Resources

About