Myo5a, encoding myosin VA, is a key protein involved in intracellular transport processes. It plays a crucial role in melanosome transport, which is essential for pigmentation in various organisms [4,5]. Myosin VA is also likely involved in other cellular trafficking events, affecting a range of biological functions.

In head and neck squamous carcinoma (HNSC), Myo5a is overexpressed, promoting cell migration in vitro, potentially through vimentin regulation. High Myo5a-expressing HNSC shows low tumor-infiltrating lymphocytes, suggesting its involvement in immune infiltration processes [1]. In laryngeal squamous cell carcinoma, overexpression of serum Myo5a predicts cervical nodal occult metastasis and poor prognosis, and miR-145 can inhibit Myo5a to suppress cancer cell proliferation and invasion [7]. In esophageal squamous cell carcinoma, circFNDC3B promotes cancer progression by targeting Myo5a via miR-370-3p/miR-136-5p [8]. In melanoma, a novel MYO5A-BRAF fusion was reported in a fatal case [3], and in pediatric low-grade glioma, a MYO5A::FGFR1 fusion was found [2]. Also, a MYO5A-NTRK3 fusion was detected in a case of central nervous system ganglioneuroblastoma [6]. In mice, novel mutations in Myo5a cause a dilute coat color phenotype due to deficient melanosome transport [4], and in a miniature Dachshund, a frameshift variant in Myo5a led to coat color dilution and neurological defects similar to human Griscelli Syndrome Type 1 [5].

In conclusion, Myo5a is crucial for pigment-related biological functions, as shown by studies in mice and dogs. In cancer research, its involvement in multiple types of carcinomas, such as head and neck, laryngeal, and esophageal squamous cell carcinomas, and its role in fusion events in melanoma, glioma, and ganglioneuroblastoma, provides insights into cancer-related biological processes. These findings from various research models, including gene-associated phenotype studies in animals, contribute to understanding Myo5a's function in normal and disease-related conditions.

References:

1. Xing, Juanli, Gu, Yanan, Song, Yichen, Ma, Junchi, Sui, Fang. 2023. MYO5A overexpression promotes invasion and correlates with low lymphocyte infiltration in head and neck squamous carcinoma. In BMC cancer, 23, 1267. doi:10.1186/s12885-023-11759-5. https://pubmed.ncbi.nlm.nih.gov/38129784/

2. Galvin, Robert T, Zheng, Cynthia, Fitzpatrick, Garrett, Chen, Liam, Moertel, Christopher L. 2023. MYO5A::FGFR1 represents a novel fusion event in pediatric low-grade glioma. In Neuro-oncology advances, 5, vdad017. doi:10.1093/noajnl/vdad017. https://pubmed.ncbi.nlm.nih.gov/37025756/

3. Clark, Hannah E, Huang, Yuan Yu Michael, Vance, Gail H, Alomari, Ahmed K. 2022. Fatal melanoma with a novel MYO5A-BRAF fusion and small associated conventional nevus: A case report and review of literature. In Journal of cutaneous pathology, 49, 808-812. doi:10.1111/cup.14263. https://pubmed.ncbi.nlm.nih.gov/35596628/

4. Zhang, Hui, Wu, Zhongping, Yang, Lijuan, Chen, Hao, Ren, Jun. . Novel mutations in the Myo5a gene cause a dilute coat color phenotype in mice. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 35, e21261. doi:10.1096/fj.201903141RR. https://pubmed.ncbi.nlm.nih.gov/33715225/

5. Christen, Matthias, de le Roi, Madeleine, Jagannathan, Vidhya, Becker, Kathrin, Leeb, Tosso. 2021. MYO5A Frameshift Variant in a Miniature Dachshund with Coat Color Dilution and Neurological Defects Resembling Human Griscelli Syndrome Type 1. In Genes, 12, . doi:10.3390/genes12101479. https://pubmed.ncbi.nlm.nih.gov/34680875/

6. Ito, Jumpei, Nakano, Yoshiko, Shima, Haruko, Ichimura, Koichi, Shimada, Hiroyuki. 2020. Central nervous system ganglioneuroblastoma harboring MYO5A-NTRK3 fusion. In Brain tumor pathology, 37, 105-110. doi:10.1007/s10014-020-00371-1. https://pubmed.ncbi.nlm.nih.gov/32556925/

7. Zhao, Xudong, Zhang, Wei, Ji, Wenyue. 2018. MYO5A inhibition by miR-145 acts as a predictive marker of occult neck lymph node metastasis in human laryngeal squamous cell carcinoma. In OncoTargets and therapy, 11, 3619-3635. doi:10.2147/OTT.S164597. https://pubmed.ncbi.nlm.nih.gov/29950866/

8. Song, Dan, Ye, Ziqi, Chen, Fangyu, Zhan, Liangliang, Sun, Xinchen. 2023. circFNDC3B promotes esophageal squamous cell carcinoma progression by targeting MYO5A via miR-370-3p/miR-136-5p. In BMC cancer, 23, 821. doi:10.1186/s12885-023-11314-2. https://pubmed.ncbi.nlm.nih.gov/37667251/