RAC1

Rac1, also known as Ras-related C3 botulinum toxin substrate 1, is a is_associated_with::protein found in human cells. It is encoded by the RAC1 is_associated_with::gene. This gene can produce a variety of alternatively spliced versions of the Rac1 protein, which appear to carry out different functions.

Function
Rac1 is a small (~21 kDa) signaling is_associated_with::G protein (more specifically a is_associated_with::GTPase), and is a member of the Rac subfamily of the family is_associated_with::Rho family of GTPases. Members of this superfamily appear to regulate a diverse array of cellular events, including the control of is_associated_with::cell growth, cytoskeletal reorganization, and the activation of protein is_associated_with::kinases.

Rac1 is a is_associated_with::pleiotropic regulator of many cellular processes, including the cell cycle, cell-cell adhesion, is_associated_with::motility (through the actin network), and of is_associated_with::epithelial differentiation (proposed to be necessary for maintaining epidermal stem cells).

Role in cancer
Along with other subfamily of Rac and Rho proteins, they exert an important regulatory role specifically in cell motility and cell growth. Rac1 has ubiquitous tissue expression, and drives cell motility by formation of is_associated_with::lamellipodia. In order for cancer cells to grow and invade local and distant tissues, deregulation of cell motility is one of the hallmark events in cancer cell invasion and metastasis. Activating or gain-of-function mutations of Rac1 are shown to play active roles in promoting mesenchymal-type of cell movement assisted by is_associated_with::NEDD9 and is_associated_with::DOCK3 protein complex. Such abnormal cell motility may result in is_associated_with::epithelial mesenchymal transition (EMT) – a driving mechanism for tumor metastasis as well as drug-resistant tumor relapse.

Clinical significance
Activating mutations in Rac1 have been recently discovered in large-scale genomic studies involving is_associated_with::melanoma  and is_associated_with::non-small cell lung cancer. As a result, Rac1 is considered a therapeutic target for many of these diseases.

A few recent studies have also exploited targeted therapy to suppress tumor growth by pharmacological inhibition of Rac1 activity in metastatic melanoma and liver cancer as well as in human breast cancer. For example, Rac1-dependent pathway inhibition resulted in the reversal of tumor cell phenotypes, suggesting Rac1 as a predictive marker and therapeutic target for trastuzumab-resistant breast cancer.

Interactions
RAC1 has been shown to interact with:
 * is_associated_with::ARFIP2,
 * is_associated_with::ARHGDIA,
 * is_associated_with::BAIAP2,
 * is_associated_with::FHOD1,
 * is_associated_with::FMNL1,
 * is_associated_with::IQGAP1,
 * is_associated_with::IQGAP2,
 * is_associated_with::Myd88,
 * DMPK,
 * is_associated_with::NCKAP1,
 * is_associated_with::PAK1,
 * is_associated_with::PAK3,
 * is_associated_with::PARD6A,
 * is_associated_with::PARD6B,
 * RICS
 * is_associated_with::STAT3, and
 * TIAM1.