Tumor cells have been known to have a tendency of invading the surrounding tissues or metastasizing themselves to distant sites other than their original site. They are known to have altered signaling pathways that thatch to cytoskeleton migration and also activation of the same. The MicroRNA-21 also known as the miR-21, has been in a significant number of times been successfully related to the uncontrollable development of solid tumors progressing in cancer patients. The interaction of Matrix hyaluronic, the HA-CD44 primary receptor with the kinase c-Jun N-Terminal lead promote the miR-12 expression through c-Jun nuclear transcription and translocation that has been activated by CD44 binding with HA. In breast cancer cells, the expression of miR-21 is c-Ju dependent where the combination of CD44 and HA develop increased Bcl-2 protein and inhibitors of the same. HA-CD44 combination therefore does promote miR-21 expression process and c-Jun signaling pathways that in turn cause chemo-resistance in breast cancer cells.
The tendency of tumor cells to metastasize primarily cause the state of morbidity in many cancer patients. The growth, migration and consequent invasion of the breast cancer cells to the surrounding tissues is connected to the cytoskeleton function. The basic process that underline these developments in tumor cell, breast cancer cells, are purposed to be the basic molecular processes that have yet been sufficiently understood by scientists. The binding of CD44 to the receptor HA have been conclude to be the abuse of adhesion of cells to the extra cellular matrix components that do stimulate various functions for the tumor-cells such as migration, survival, growth, invasion and even cytoskeleton activation (Schooneveld, 2015). HA and CD44 have on frequent times been sighted in high concentrations in tumor cell area and therefore related to malignancy of tumor cells and their tendency to invade the surrounding tissues. HA plays significant role in regulating CD44 signaling and tumor cells oncogeneses. They play a significant role in activation for the RhoA signaling and Rho-Kinase function during cell invasion and migration to surrounding tissues. They also regulate the miR-10b inflating and the consequent activation of RhoGTpase/ROK. They are considered to have a main role in miR-21 regulation and the consequent chemotherapy resistance that the tumors develop against any medical chemical that they encounter in their migration and invasion process in breast cancer cells (Chen, 2014). The combination of CD44 and HA affects not only the cellular adhesion of tumor cells but also does stimulate their cell-specific function such as invasion that lead to the uncontrollable progression of breast cancer cells. In summary, HA-CD44 combination therefore does promote miR-21 expression process and c-Jun signaling pathways that in turn cause chemo-resistance in breast cancer cells (Chen, 2014).
The activation of RhoA has been seen to induce the protrusion of cell membrane mostly in tumor epithelial cells. This process is assisted with the participation of RhoC in transforming the cytoskeleton. The RhoA/RhoC activation is redirected t the combination of HA and CD44 that result to the accumulation of the RhoA and RhoC that have been related to breast tumor cell invasion and its metastasis (Schooneveld, 2015). Rho-Kinase enzyme that is developed from interaction of CD44 and Rho-specific guanine nucleotide, is responsible for the regulation of the cytoskeleton through phosphorylation of various important cytoskeleton regulators. This subsequently leads to cytoskeleton activation that id followed by migration of the tumor cell and invasion of the surrounding tissues in breast cancer patients. ROK is usually overexpressed in breast cancer cells that sees to it that there are capabilities of the breast cancer cells to phosphorylate leading to breast cancer cellular transformation due to cytoskeletal changes. CD44 interaction with ROK enhances its binding capacity.
MicroRNAs inhibit transfers of miRNAs to seed regions. MiRNAs are normally located in cancer-related genomic regions in the breast cancer site. The direct target if Kruppel-like factor by miR-10b affects the tumor cells in breast cancer. The metastasis and invasion of a tumor cell to sorrowing tissues is directly related to miR-10b that entails these processes. Metastasis for instance can be silenced through the reduction of miR-10b concertation around the tumor cells in breast cancer patients leading to reduced invasion and consequent progression of breast cancer cells. MiR-10b is obtained from the combination of HA and CD44, miR-10b also affects the RhoGTPase-ROK signaling that activates tumor cells (Bourguignon, 2012).
HA-CD44 also regulates the signaling of miR-21 in sites that are located with tumor breast cancer. These play a significant role of drug resistance as the generated mobilization by HA-CD44 combination. The interaction of HAD and CD44 influences the mobilization of Ca2+ Nanog signaling cytoskeletal activation and the activation of EGFR (Bourguignon, 2012). It is therefore concluded that the integration of HA and CD44 is involved in the transformation of tumor cells into chemo-resistant cells that therefore resist drug chemicals meant to kill them. They instead are directly involved in the transformation of tumor cells into multi-drug resistant cells.
Summary and Conclusion
Activation of RhoGTPases into areas of tumor cells such as breast cancer causes activation of RhoA and RhoC and ROK kinase that are associated with the production of structural changes in cellular cell growth, cytoskeleton reorganization and cell-specific activities such as migration, invasion and survival of the tumor cells in breast cancer and therefore causing progression of the cancer in the patients suffering from it. A significant volume of assays have been formulated on the effect of the HA and CD44 combination including Anti-miR-21 preparation immunoblotting techniques, immunofluorescent staining, and even chromatin immunoprecipitation assays has been formulated on the effects of the combination of HA and CD44
Bourguignon, L. Y. (2012). Hyaluronan-CD44 interaction promotes microRNA signaling and RhoGTPase activation leading to tumor progression. Small GTPases, 3(1), 53-59.
Chen, L., & Bourguignon, L. Y. (2014). Hyaluronan-CD44 interaction promotes c-Jun signaling and miRNA21 expression leading to Bcl-2 expression and chemoresistance in breast cancer cells. Mol Cancer, 13(52.10), 1186.
Van Schooneveld, E., Wildiers, H., Vergote, I., Vermeulen, P. B., Dirix, L. Y., & Van Laere, S. J. (2015). Dysregulation of microRNAs in breast cancer and their potential role as prognostic and predictive biomarkers in patient management. Breast Cancer Research, 17(1), 21.
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