Understanding The Role Of Growth factors And Their Receptors In Regulating The Epithelial To Mesenchymal Transition And Invasion Of Ovarian Cancer Cells.
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Understanding The Role Of Growth factors And Their Receptors In Regulating The Epithelial To Mesenchymal Transition And Invasion Of Ovarian Cancer Cells.
|
|
| Creator |
Bhattacharya, Rahul
|
|
| Subject |
Cell Biology & Physiology
|
|
| Description |
Ovarian cancer is the third most leading type of cancer among women in India. The major drawback of ovarian cancer is its detection at an advanced stage, whence the tumor has already metastasized (stage IIIc). This stage involves the spread of the cancer cells across the lymph nodes into the upper abdomen and the treatment regimen of these patients involves surgical removal of the tumor followed by systemic chemo-and radio-therapy. Thwarting the metastatic behavior along with early detection are thus the major challenges in combatting this aggressive type of cancer.
The metastatic behavior of cancers depends on the invasive/migratory properties of the tumor cells. During metastasis the tumor cells enter into the bloodstream and invade to a secondary site. The process of Epithelial-Mesenchymal transition (EMT) governs the invasive/metastatic behavior of different cancer types including ovarian cancer. The spindle shaped morphology of the cells attained by virtue of rearrangement of actin-cytoskeleton during EMT promotes the invasive behavior of tumor cells. The process of EMT is governed by a plethora of growth-factor signaling cascades. Enhanced growth factor functioning by virtue of upregulation of the growth factors or their receptors is one of prominent features of cancer cells. In fact, differential splicing of the receptors also contributes to the amplification of growth-factor mediated signaling. Apart from the well documented transcriptional regulation of EMT, alternative splicing has been implicated in the modulation of this trans-differentiation process. EMT is accompanied by alterations in the repertoire of splice isoforms which in turn modulate each of cancer hallmarks. Different growth factor signaling pathways and transcription factors have been involved in the regulation of these splicing changes which ultimately facilitate cancer metastasis.
We have tried to address these issues in this thesis by designing proper model systems and performing numerous experiments to shed light into the mechanisms governing ovarian cancer metastasis. This thesis is comprised of three chapters: Chapter I deals with the interaction among two growth factor (FGF and VEGF) families and their contribution towards ovarian cancer metastasis. In this study, we have explored the mechanism governing the augmentation of VEGF and its main receptor in ovarian cancer cells and its impact in modulating the invasive behavior of the cells. Chapter II elucidates mechanism governing the splice isoform switching of Fibroblast growth factor receptors and the roles of these splice variants in regulating EMT/invasion of ovarian cancer cells. This study depicts that a growth factor (FGF2) modulates the isoform switching of its own receptor (FGFR2) to promote autocrine signaling which enhances the metastatic potential of ovarian cancer cells. Chapter III concerns a co-receptor molecule, CD44, which is differentially spliced in ovarian cancer cells. Precisely, this study depicts growth factor (TGFβ1/Activin-A) induced EMT involves the splice isoform switching of CD44. This splicing switch in turn, modulated the metastatic properties of ovarian cancer cells. Therefore, we have explored some of the undeciphered mechanisms which promote the metastatic properties of ovarian cancer. Since enhanced invasion/metastasis render lethality to ovarian cancer, our work and future works in this direction might be useful in developing therapies to combat this aggressive gynaecological disease.
|
|
| Date |
2018
|
|
| Type |
Thesis
NonPeerReviewed |
|
| Format |
application/pdf
|
|
| Identifier |
http://www.eprints.iicb.res.in/2751/1/Merged_Thesis_complete.pdf
Bhattacharya, Rahul (2018) Understanding The Role Of Growth factors And Their Receptors In Regulating The Epithelial To Mesenchymal Transition And Invasion Of Ovarian Cancer Cells. PhD thesis, University of Calcutta. |
|
| Relation |
http://www.eprints.iicb.res.in/2751/
|
|