The Cytoskeletal Protein Cyclase-Associated Protein 1 (CAP1) in Breast Cancer: Context-Dependent Roles in Both the Invasiveness and Proliferation of Cancer Cells and Underlying Cell Signals

• Published in: International journal of molecular sciences Vol. 20; no. 11; p. 2653
• Main Authors: Hasan, Rokib, Zhou, Guo-Lei
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30-05-2019; MDPI
• Subjects: Actin; Actin Cytoskeleton - metabolism; Animals; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; CAP1; Cell activation; Cell adhesion; Cell adhesion & migration; Cell Adhesion - genetics; Cell Cycle Proteins - chemistry; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; cell invasiveness; Cell Movement - genetics; Cell Proliferation; Cytoskeletal Proteins - chemistry; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; Cytoskeleton; Depletion; Enzymes; ERK; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - metabolism; FAK; Female; Focal adhesion kinase; Gene expression; Humans; Insects; Invasiveness; Kinases; Mammals; Metastases; Phenotypes; Protein Binding; Proteins; Rap1 protein; Review; Roles; Signal Transduction; Structure-Activity Relationship; Studies; the actin cytoskeleton; Translational Research, Biomedical; Yeast; United States > US; Arkansas; CAP1; FAK; cell invasiveness; cell proliferation; cell adhesion; breast cancer; ERK; the actin cytoskeleton
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20112653

As a conserved actin-regulating protein, CAP (adenylyl Cyclase-Associated Protein) functions to facilitate the rearrangement of the actin cytoskeleton. The ubiquitously expressed isoform CAP1 drives mammalian cell migration, and accordingly, most studies on the involvement of CAP1 in human cancers have largely been based on the rationale that up-regulated CAP1 will stimulate cancer cell migration and invasiveness. While findings from some studies reported so far support this case, lines of evidence largely from our recent studies point to a more complex and profound role for CAP1 in the invasiveness of cancer cells, where the potential activation of cell adhesion signaling is believed to play a key role. Moreover, CAP1 was also found to control proliferation in breast cancer cells, through the regulation of ERK (External signal-Regulated Kinase). Alterations in the activities of FAK (Focal Adhesion Kinase) and ERK from CAP1 depletion that are consistent to the opposite adhesion and proliferation phenotypes were detected in the metastatic and non-metastatic breast cancer cells. In this review, we begin with the overview of the literature on CAP, by highlighting the molecular functions of mammalian CAP1 in regulating the actin cytoskeleton and cell adhesion. We will next discuss the role of the FAK/ERK axis, and possibly Rap1, in mediating CAP1 signals to control breast cancer cell adhesion, invasiveness, and proliferation, largely based on our latest findings. Finally, we will discuss the relevance of these novel mechanistic insights to ultimately realizing the translational potential of CAP1 in targeted therapeutics for breast cancer.