Silencing profilin-1 inhibits endothelial cell proliferation, migration and cord morphogenesis

Ding, Zhijie; Lambrechts, Anja; Parepally, Mayur; Roy, Partha

doi:10.1242/jcs.03268

Cited by 94 publications

(88 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In general, highly invasive tumour cells like MDA-MB-231 are weakly adherent in nature and thus, contractility may be of much lesser significance in the context of motility of these cells when compared to some of the more strongly adherent cell types, such as vascular endothelial cells. A noteworthy point here is that in our previous study we observed a dramatic decrease in actin stress-fibres and FAs (the molecular machineries for generating cell contractility) in vascular endothelial cells after silencing Pfn1, which could partly account for their translocation defect (Ding et al, 2006). Among its diverse functions, Pfn1 has been most heavily implicated in actin-based cell protrusion.…”

Section: Discussionmentioning

confidence: 60%

“…Although further mechanistic studies are needed to elucidate why Pfn1 depletion increases motility in breast cancer cells, yet dramatically inhibits motility of other cell types, such as vascular endothelial cells (Ding et al, 2006), certain speculations may be appropriate. First, whether Pfn1 would inhibit or facilitate actin polymerisation depends on its concentration relative to G-actin and uncapped barbed ends of actin filaments.…”

Section: Discussionmentioning

confidence: 99%

“…In gene silencing experiments, cells were transfected with either a control siRNA or a custom-designed Pfn1-siRNA as previously described (Ding et al, 2006).…”

Section: Cell Culture and Transfectionmentioning

confidence: 99%

“…Wound-healing experiments were performed as previously described (Ding et al, 2006). Width of the wound for any field of observation was measured at 3 -4 different locations.…”

Section: Cell Motility and Invasion Assaysmentioning

confidence: 99%

“…A large number of pathogenbased model studies have implied Pfn1's function in actin-based protrusion during cell migration Mimuro et al, 2000;Grenklo et al, 2003). A more direct evidence of Pfn1's importance in mammalian cell migration, particularly for its role in cell protrusion, has been recently demonstrated in human vascular endothelial cells by our group (Ding et al, 2006). Given these findings, it is thus not clear why Pfn1 expression is significantly downregulated in different types of invasive cancer cells.…”

mentioning

confidence: 97%

See 4 more Smart Citations

Profilin-1 is a negative regulator of mammary carcinoma aggressiveness

et al. 2007

View full text Add to dashboard Cite

Expression of profilin-1 (Pfn1) is downregulated in breast cancer cells, the functional significance of which is yet to be understood. To address this question, in this study we evaluated how perturbing Pfn1 affects motility and invasion of breast cancer cells. We show that loss of Pfn1 expression leads to enhanced motility and matrigel invasiveness of MDA-MB-231 breast cancer cells. Interestingly, silencing Pfn1 expression is associated with downregulation of both cell -cell and cell -matrix adhesions with concomitant increase in motility and dramatic scattering of normal human mammary epithelial cells. Thus, these data for the first time suggest that loss of Pfn1 expression may have significance in breast cancer progression. Consistent with these findings, even a moderate overexpression of Pfn1 induces actin stress-fibres, upregulates focal adhesion, and dramatically inhibits motility and matrigel invasiveness of MDA-MB-231 cells. Using mutants of Pfn1 that are defective in binding to either actin or proline-rich ligands, we further show that overexpressed Pfn1 must have a functional actin-binding site to suppress cell motility. Finally, animal experiments reveal that overexpression of Pfn1 suppresses orthotopic tumorigenicity and micro-metastasis of MDA-MB-231 cells in nude mice. These data imply that perturbing Pfn1 could be a good molecular strategy to limit the aggressiveness of breast cancer cells.

show abstract

Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

“…In gene silencing experiments, cells were transfected with either a control siRNA or a custom-designed Pfn1-siRNA as previously described (Ding et al, 2006).…”

Section: Cell Culture and Transfectionmentioning

confidence: 99%

“…Wound-healing experiments were performed as previously described (Ding et al, 2006). Width of the wound for any field of observation was measured at 3 -4 different locations.…”

Section: Cell Motility and Invasion Assaysmentioning

confidence: 99%

mentioning

confidence: 97%

See 3 more Smart Citations

Profilin-1 is a negative regulator of mammary carcinoma aggressiveness

et al. 2007

View full text Add to dashboard Cite

show abstract

Profilin upregulation induces autophagy through stabilization of AMP‐activated protein kinase

Saurav

Manna

2022

FEBS Letters

View full text Add to dashboard Cite

Profilin regulates actin polymerization, and its balanced expression is required for cellular growth and development. Most tumours have compromised profilin expression, and its overexpression in MDA MB-231 breast cancer cells has been reported to activate AMP-activated protein kinase a (AMPKa), an energy-sensing molecule that affects various cellular processes including autophagy. This study aims to explore the role of profilin in autophagy induction. We employed all-trans retinoic acid (ATRA) as an inducer of profilin expression and showed that profilin induces autophagy through mTOR inhibition, autophagy-activating kinase ULK1 upregulation, and AMPK stabilization as well as its activation. Furthermore, evidence from our study indicates physical interaction between profilin and AMPK, which results in AMPK stabilization and induction of prolonged autophagy, thereby leading to apoptosis. This study uncovers a novel mechanism that induces autophagy in triple-negative breast cancer cells.

show abstract

Profilin‐1 overexpression restores adherens junctions in MDA‐MB‐231 breast cancer cells in R‐cadherin‐dependent manner

Zou

Hazan

Roy

2009

Cell Motil. Cytoskeleton

Self Cite

View full text Add to dashboard Cite

Profilin-1 (Pfn1), a ubiquitously expressed actin-binding protein, is downregulated in several different types of adenocarcinoma and elicits tumor-suppressive effect on breast cancer cell lines. MDA-MB-231 (MDA-231), a breast cancer cell line that displays all the characteristics of postepithelial-to-mesenchymal transition and does not form cell-cell adhesion, can be reverted to an epithelioid phenotype by Pfn1 overexpression. This morphological transition is caused by restoration of adherence junctions (AJ) requiring Pfn1's interaction with actin. Pfn1 overexpression increases the expression level of R-cadherin (a type of cadherin that is endogenously expressed in the parental cell line) and restores AJ in MDA-231 cells in R-cadherin dependent manner. These findings highlight important role of Pfn1 in the regulation of epithelial cell-cell adhesion.

show abstract

Silencing profilin-1 inhibits endothelial cell proliferation, migration and cord morphogenesis

Cited by 94 publications

References 0 publications

Profilin-1 is a negative regulator of mammary carcinoma aggressiveness

Profilin-1 is a negative regulator of mammary carcinoma aggressiveness

Profilin upregulation induces autophagy through stabilization of AMP‐activated protein kinase

Profilin‐1 overexpression restores adherens junctions in MDA‐MB‐231 breast cancer cells in R‐cadherin‐dependent manner

Contact Info

Product

Resources

About