Table 3.
Anti-cancer drugs which target the cytoskeletal proteins to alter or inhibit EMT in cancer therapy. The associated cancers and drugs which are resistant to these cancers are also laid out.
| Target Cytoskeletal Proteins | Features | Functions | Anti-Cancer Drugs | Function of Anti-Cancer Drugs |
Associated Cancers | Drugs Resistant to These Cancers |
|---|---|---|---|---|---|---|
| Vimentin | Central intermediate filament (IF) protein of mesenchymal cells | Organizer of several critical proteins involved in attachment, migration, and cell signaling | Moscatilin FiVe1 |
Inhibits EMT and sensitizes anoikis FiVe1 disrupts mitotic progression |
Lung cancer [179,180] Brest cancer [181] |
|
| α-Actinin | Cellular protrusions, stress fibers, lamellipodia, microvilli, invadopodia of multiple cell types | Crosslinks actin into parallel bundles by forming dimers head to tail | Not Available clinically | Expression in breast, ovary, pancreas, lung, astrocytoma cancers. [55,215,216,217,218,219,220] | Docetaxel, carboplatin, tamoxifen (Ovary and breast) [221,222] | |
| γ-actin | Distributed along perinuclear and nearby cytoplasm, suggesting a distribution based on diffusion or restriction to nearby cytoplasm. [223] | Regulates cellular morphologies, extending processes, and ruffling edges that reflect cell movement [223] | Not Available clinically | Acute lymphoblastic leukemia | Vinblastine, Desoxyepothilone [224] | |
| Distributes β-actin and form actin-rich retraction fibers during mitosis | Paclitaxel | Targets the microtubule and causes mitotic arrest and apoptosis | Breast cancer [225] | |||
| Neuroblastoma | Paclitaxel, vinblastine, epothilone [224] | |||||
| F-actin | Formed by the polymerization of G-actin under physiological conditions, with the concomitant hydrolysis of ATP. | Cell adhesion, migration, and division | Jasplakinolide (Jas) | Stimulates actin polymerization but disrupts F-actin fibers | Breast and prostate cancer [226,227] | |
| Eplin | Stress fibers of multiple cell types | Actin filament bundling and side-binding | Not Available clinically | Downregulation correlates with progression and metastasis in prostate cancer. Potential tumor suppressor in breast cancer [228,229,230] | ||
| β-Tubulin | polymerize into microtubules, a significant component of the eukaryotic cytoskeleton |
Involved in many essential cellular processes, including mitosis | Taxanes (paclitaxel), epothilones, and Vinca alkaloids | Binds to β-tubulin and disrupts microtubule dynamics by inducing a potent mitotic block and subsequent cell deathVinca alkaloids inhibit MT polymerization. | Breast, ovarian, lung cancer [212] | |
| Acute lymphoblastic leukemia | Vincristine, vinblastine and desoxyepothilone B [231,232] | |||||
| Non-small cell lung cancer | Paclitaxel [233] | |||||
| Cytoskeleton-associated protein 5 (CKAP5) | A microtubule-associated protein which is encoded by the CKAP5 gene | Regulates microtubule organization, nucleation, elongation, and microtubule dynamics by binding to the plus end of the microtubule. Serves as a cell surface target for T-DM1 | T-DM1 | Upon forming the T-DM1-CKAP5 complex, cell membrane damage occurs, which leads to calcium influx, disrupting microtubule dynamics causing apoptosis | Heptocellular carcinoma [214] |