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Abikar, A.

Publications and source records attributed to Abikar, A..

4 recordsLinked to original sources

ECM (collagen) mediated signaling drives the emergence of androgen independence in prostate cancer cells

The extracellular matrix is a dynamic entity that undergoes continuous deposition, remodeling, and degradation to maintain tissue homeostasis. As a major structural component of the tumor microenvironment, the ECM plays crucial roles in providing mechanical support, modulating the microenvironment, and serving as a reservoir for signaling molecules. Tissue stiffness is primarily determined by the abundance and cross-linking of the ECM components. Collagen is one of the major components of ECM and contributes to 30% of the total ECM. Increased collagen deposition contributes to enhanced tissue stiffness and is associated with a more aggressive cancer phenotype. A restructured ECM, particularly collagen content, can influence cellular signaling pathways through interaction with cell surface receptors. In the current study, we investigated the role of collagen in prostate cancer. Our findings indicate that collagen, a major component of the TME, modulates prostate cancer cell migration, alters sensitivity to chemotherapeutic agents, and promotes non-genomic activation of androgen receptor signaling through FAK activation, thereby contributing to therapy (androgen deprivation therapy) resistance and cancer progression.

cancer biology↗

Secretome analysis of cancer-associated fibroblasts from prostate cancer to identify potential therapeutic targets

Tumor microenvironment (TME) is a complex entity comprising of several cell types secreted factors as well as an extracellular matrix. A dynamic interaction between tumor cells and their environment profoundly influences tumor survival, aggressiveness, and progression. Cancer- associated fibroblasts (CAFs) are one of the major cellular components of TME and serve as a major source of various secreted factors. These factors are known to modulate tumor survival and progression, as well as their response to therapy. Despite the importance of the TME factors on various aspects of tumor cell behavior, to date factors unique to CAFs that could be potential therapeutic targets are not identified in most systems. This study was aimed at identifying such factors from CAFs which may impact tumor behavior such as the ability to metastasize, response to therapy, relapse, etc. This would aid in identifying therapeutic targets originating from the TME. Furthermore, targeting those factors along with conventional chemotherapeutic drugs is likely to enhance the overall efficacy of the therapy. This study has used fibroblasts derived from Benign Prostatic Hyperplasia (BPH) and prostate cancer for comparing the secretome using a quantitative proteomics approach. 66 proteins unique to CAFs and 24 unique to control (BPH) fibroblasts have been identified. Besides 236 proteins are differentially expressed between control and cancer- associated fibroblasts. Using in-silico approaches the potential processes that may be influenced by the differentially expressed proteins have also been identified. This study has identified both qualitative and quantitative differences between the secretomes of normal and cancer-associated fibroblasts with further validation, this paves the way for identifying therapeutic targets.

cancer biology↗

Comparative transcriptome of normal and cancer- associated fibroblasts

The characteristics of a tumor are largely determined by its interaction with the surrounding micro-environment (TME). TME consists of both cellular and non-cellular components. Cancer associated fibroblasts (CAFs) are a major component of the TME. They are a source of many secreted factors that influence the survival and progression of tumors as well as their response to drugs. Identification of markers either overexpressed in CAFs or unique to CAFs would pave the way for novel therapeutic strategies that would combine conventional chemotherapy and TME-targeted therapy for a better outcome. We have used fibroblast derived from Benign Prostatic Hyperplasia (BPH) and prostate cancer to perform a transcriptome analysis in order to get a comparative profile of normal and cancer-associated fibroblasts. This has identified 818 differentially expressed mRNAs and 17 lincRNAs between normal and cancer-associated fibroblasts.

cancer biology↗

microRNA profile of endometrial cancer from Indian patients-Identification of potential biomarkers for prognosis

Endometrial cancer is one of the major cancers in women throughout the world. If diagnosed early, these cancers are treatable and the prognosis is usually good. However, one major problem in treating endometrial cancer is accurate diagnosis and staging. Till date, the choice method for diagnosis and staging is histopathology. Although there are few molecular markers identified, they are not always sufficient in making accurate diagnosis and deciding on therapeutic strategy. As a result, very often patients are under treated or over treated. In this study, our group has profiled microRNAs (miRNA) from Indian patients using NGS-based approach. We have identified differentially expressed microRNAs in endometrial cancer. These microRNAs have also been compared to data from TCGA (The Cancer Genome Atlas), which represent other populations and also correlated to relevance in overall survival. Using in-silico approaches, mRNA targets of the miRNAs have been predicted. After comparing with TCGA, we have identified 16 miRNA-mRNA pairs which could be potential prognostic biomarkers for endometrial cancer. This is the first miRNA profiling report from Indian cohort and one of the very few studies which have identified potential biomarkers of prognosis in endometrial cancer.

cancer biology↗