Fam163a, also called neuroblastoma-derived secretory protein (NDSP) or C1ORF76, is located on chromosome 1q25.2. It has been implicated in multiple biological processes. In the ERK signaling pathway, it acts as a positive regulator, promoting cell proliferation. It also may be part of the mitochondrial proteome, potentially playing a role in mitochondrial-related functions [1,2].

In squamous cell lung carcinoma, Fam163a overexpression increases ERK and p90RSK phosphorylation, promotes cyclin D1 expression, and directly interacts with 14-3-3β and ERK, regulating ERK phosphorylation by upregulating 14-3-3β protein levels. Its expression correlates with larger tumor size, TNM staging, and regional lymph node metastasis, and patients with positive expression have shorter survival times [1]. In hypothalamic arcuate nucleus, Fam163a knockdown increases short-term food intake, reduces leptin levels, and decreases the firing frequency of AgRP neurons, while also differentially regulating mitochondrial-related gene expression [2].

In conclusion, Fam163a has important functions in cell proliferation and mitochondrial-related processes. Its role in promoting cell proliferation in squamous cell lung carcinoma and modulating AgRP neuron activity in the hypothalamus through mitochondrial-related mechanisms, as revealed by in vivo studies, indicates its significance in cancer and metabolism-related disease areas.

References:

1. Liu, Nan, Zhou, Haijing, Zhang, Xiupeng, Li, Ailin, Miao, Yuan. 2019. FAM163A, a positive regulator of ERK signaling pathway, interacts with 14-3-3β and promotes cell proliferation in squamous cell lung carcinoma. In OncoTargets and therapy, 12, 6393-6406. doi:10.2147/OTT.S214731. https://pubmed.ncbi.nlm.nih.gov/31496741/

2. Erdogan, Cihan Suleyman, Yavuz, Yavuz, Ozgun, Huseyin Bugra, Kalkan, Ugur Faruk, Yilmaz, Bayram. . Fam163a knockdown and mitochondrial stress in the arcuate nucleus of hypothalamus reduce AgRP neuron activity and differentially regulate mitochondrial dynamics in mice. In Acta physiologica (Oxford, England), 241, e70020. doi:10.1111/apha.70020. https://pubmed.ncbi.nlm.nih.gov/40071489/