My current research goal is to decipher the mechanism by which immune cells-derived exosomes mediate long distant
communication with secondary tissues to promote metastasis as a basis to develop cancer biomarkers and
exosome-based targeted therapy. Thus, my research path encompassing two major research themes in exosomes
medical research:
1. Cancer biomarkers: The use of exosomes by means of liquid biopsy to develop tumor diagnostic and prognostic
markers.
2. Cancer Therapeutics: The role of exosomes in reprogramming distant organ's stromal cells to form premetastatic
niche as a basis to develop exosome-based targeted therapy in cancer.
It is becoming widely accepted that immune cells contribute to a very large extent to the tumor progression. For example, Macrophages have been shown to increase tumor growth in a mechanism similar to that seen in wound tissue repair and healing process. Another very interesting line of evidence recently emerged implicates Neutrophils, the first line immune system defense, in increase cancer progression through neutrophils extra cellular traps (NETs). NETs are formed when activated neutrophils release their chromatin and granular content and form mesh network of DNA and different degrading enzymes and proteins to trap pathogens in acute phase injury or infections. NETs have been recently identified as one of the most significant key players in promoting tumor progression. Interestingly, neutrophils have been reported to undergo phenotype transition in what so-called N2 neutrophils that can strengthen cancer resistance to harsh environment and increase its survival. In the current research, we are trying to understand the role of neutrophils in the the progression of peritoneal carcinosis PC in vivo. We developed a PC model and now NETs role is evaluated on different aspects including the impact on tumor cell migration and adhesion as a potential therapeutic target to prevent PC.
MiR-155 is overexpressed in different types of tumors, including colon cancer. High expression of miR-155 has been correlated with poor prognosis in colorectal cancer patients suggesting a pro-carcinogeneic role of miR-155. Increased RNA translation induced by miRNAs has been shown to be mediated via AU-rich elements (AREs) in the 3′ untranslated region (UTR) of mRNA for instance AUUA and AUUUA, as well as adjoining non-AU sequences. Notably, investigations have reported that miR-155 can regulate migration and invasion of certain tumor cell types, such as breast, colon, pancreatic, hepatocellular and nasopharyngeal cancers. However, the role and mechanism of MiR-155 in regulating chemokine-induced colon cancer cell migration remains poorly understood. HuR has been shown to regulate RhoA, while miR-155 has been recently demonstrated to target directly RhoA in positive regulation manner in serum starved cells. RhoA belongs to a GTPase oncogenic family which has AU rich elements in the 3-UTR region. The regulation was confirmed by direct binding of miR-155-5p to these motifs (Amr A. Al-Haidari, et al. MiR-155-5p positively regulates CCL17-induced colon cancer cell migration by targeting RhoA, Oncotarget. 2017 Feb 28; 8(9): 14887–14896). Interestingly, HuR can bind RhoA in these motifs as well and this could explain at least in part the RhoA regulation by miR-155-5p and why cancer cells exploit this regulation profile in early tumorigenesisphases. In this project, we are trying to understand how HuR contributes to colon cancer metastasis.