Rac1, A Potential Target for Tumor Therapy

Abstract

RAS-related C3 botulinum toxin substrate 1 (Rac.1) is one of the important members of Rho GTPases. It is well known that Rac1 is a cytoskeleton regulation protein that regulates cell adhesion, morphology, and movement. Rac1 is highly expressed in different types of tumors, which is related to poor prognosis. Studies have shown that Rac1 not only participates in the tumor cell cycle, apoptosis, proliferation, invasion, migration and angiogenesis, but also participates in the regulation of tumor stem cell, thus promoting the occurrence of tumors. Rac1 also plays a key role in anti-tumor therapy and participates in immune escape mediated by the tumor microenvironment. In addition, the good prospects of Rac1 inhibitors in cancer prevention and treatment are exciting. Therefore, Rac1 is considered as a potential target for the prevention and treatment of cancer. The necessity and importance of Rac1 are obvious, but it still needs further study.

Regulation of local GTP availability controls RAC1 activity and cell invasion

“…Guanine nucleotide-binding proteins (or G-proteins) regulate multiple cellular processes and are observed to be hyper-activated in many human cancers 1 . While a few activating point mutations of Ras-related C3 botulinum toxin substrate 1 (RAC1), a member of the RHO-GTPases family of G-proteins, have been identified in malignancies such as melanoma, breast, and head and neck cancers 2 – 5 , the mechanisms behind the overall over-activation of GTPases in cancer has not yet been elucidated.…”

“…In the active, GTP (guanosine triphosphate)-bound, form RAC1 interacts with downstream effectors triggering activation of multiple signaling pathways ultimately resulting in regulation of cell motility, invasion, and progression through the cell cycle 2 – 6 . On the contrary, GDP-bound RAC1 is inactive.…”

Cell Signaling Pathways That Promote Radioresistance of Cancer Cells

“…Rac1 belongs to the Rho family of GTPases that play key roles in cytoskeleton reorganization, cell polarity, and cell migration [59]. Like all GTPases, Rac1 is active in its GTP-bound form and inactive in its GDP-bound form [60].…”

Application of Proteomics in the Discovery of Radiosensitive Cancer Biomarkers

“…Comparative proteomic analysis of head and neck squamous carcinoma cell lines FaDu and SCC25 with radiation-resistant cell lines FaDu-RR and SCC25-RR showed that Ras-related C3 botulinum toxin substrate 1 (Rac1) could be used as a new therapeutic target ( 52 ). Rac1 is a cytoskeleton involved in cell adhension, morphology, and movement; overexpression of Rac1 is associated with unfavorable survival in different type of cancer ( 53 ).…”