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Biology subjects

Zirmire, R. K.

Publications and source records attributed to Zirmire, R. K..

2 recordsLinked to original sources

Bacopa monnieri phytochemicals regulate fibroblast cell migration via modulation of focal adhesions

The Bacopa monnieri plant contains a large repertoire of active phytochemicals that have been used extensively in traditional medicine for the treatment of various complex diseases. More recently it has been shown to increase the wound healing rate in rats, though its mechanism of action is largely unknown. Here we investigated the cellular pathways activated by a methanol extract of Bacopa monnieri in human dermal fibroblasts, which play many critical roles in the wound healing program. Gene expression analysis revealed that Bacopa monnieri extract can enhance tissue repair by modulating multiple processes involved in the wound healing program such as migration, proliferation, and angiogenesis. We discovered that Bacopa monnieri extract can increase migration of fibroblasts via modulating the size and number of focal adhesions. Bacopa monnieri-mediated changes in focal adhesions are dependent on 5{beta}1 integrin activation and subsequent phosphorylation of Focal Adhesion Kinase (FAK). Altogether our results suggest that Bacopa monnieri extract could enhance the wound healing rate via modulating fibroblast migration in the wound bed.

cell biology↗

Snail maintains the stem/progenitor state of skin epithelial cells and carcinomas through the autocrine effect of the matricellular protein Mindin

Intratumoral heterogeneity poses a major challenge in designing effective anti-cancer strategies. Accumulating evidence suggests that this heterogeneity arises from cancer stem cells (CSCs) that also drives tumor aggressiveness and drug resistance. The stemness of CSCs are preserved by an ill-defined combination of intrinsic and external factors and is particularly intriguing since they exist within a sea of similar cells at various degrees of differentiation. In models of cutaneous squamous cell carcinoma (cSCC), we discovered a non-EMT function for the transcription factor Snail in maintaining stemness of keratinocytes. This is accomplished by the secretion of the matricellular protein Mindin from Snail expressing cells, which creates a protective niche that impedes differentiation. In an autocrine fashion, extracellular Mindin activates a Src -STAT3 pathway to reinforce the stem/progenitor phenotype and disruption of this signalling module in human cSCC attenuates tumorigenesis. The expression of Mindin in multiple carcinomas, and its critical role in cancer progression suggests that it would be a promising target for therapeutic intervention.

cell biology↗