TMEM41A, a 264-amino-acid transmembrane protein, is encoded by a gene mapped to human chromosome. It belongs to a group of transmembrane proteins involved in signaling pathways and tumor development. Although its exact normal physiological function remains to be fully elucidated, it has been implicated in processes related to lipid movement across the membrane bilayer as its homolog TMEM41B is an ER-localized lipid scramblase, and the scramblase activity of TMEM41A can be assayed [3].

In multiple cancers, TMEM41A shows abnormal overexpression and is associated with poor prognosis. In endometrial carcinoma, its overexpression can diagnose the cancer, evaluate poor prognosis, and is related to clinical features, immune microenvironment, and RNA modifications [1]. In breast cancer, TMEM41A is overexpressed, especially in early-stage and ductal A breast cancer, correlating with poor prognosis and immune cell infiltration, and is an independent risk factor [2]. In gastric cancer, it is highly expressed, associated with progression and metastasis, and knockdown in vitro and in vivo decreased cell migration by regulating epithelial-to-mesenchymal transition and autophagy via E-cadherin modulation [4]. In colorectal cancer, it interacts with C12ORF49, SREBF1, and S1PR3, contributing to poor prognosis [5].

In conclusion, TMEM41A is significantly associated with the prognosis and progression of multiple cancers such as endometrial, breast, gastric, and colorectal cancers. Its overexpression in these cancer types suggests it could potentially serve as a biomarker and therapeutic target. Functional studies, including loss-of-function experiments in cancer cells, have revealed its role in metastasis, immune-related processes, and interactions with other proteins, contributing to our understanding of cancer-associated biological processes.

References:

1. Shi, Ke, Liu, Xiao-Li, Guo, Qiang, Jiang, Ni, Li, Dan. 2023. TMEM41A overexpression correlates with poor prognosis and immune alterations in patients with endometrial carcinoma. In PloS one, 18, e0285817. doi:10.1371/journal.pone.0285817. https://pubmed.ncbi.nlm.nih.gov/37478120/

2. Fan, Fan, Feng, Ruiwen, Zhang, Yuxin, Li, Xiabin, Tang, Yan. 2024. Investigation of TMEM41A's function in breast cancer prognosis and its connection to immune cell infiltration. In Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 27, 1569-1585. doi:10.1007/s12094-024-03714-y. https://pubmed.ncbi.nlm.nih.gov/39264531/

3. Wu, Lingzhi, Liu, Lu, Xu, Bolin, Huang, Dong, Chen, Xiao-Wei. 2022. In vitro and in vivo assay of the ER lipid scramblase TMEM41B. In STAR protocols, 3, 101333. doi:10.1016/j.xpro.2022.101333. https://pubmed.ncbi.nlm.nih.gov/35496801/

4. Lin, Bin, Xue, Yingming, Qi, Chao, Chen, Xiangjie, Mao, Weizheng. 2018. Expression of transmembrane protein 41A is associated with metastasis via the modulation of E‑cadherin in radically resected gastric cancer. In Molecular medicine reports, 18, 2963-2972. doi:10.3892/mmr.2018.9241. https://pubmed.ncbi.nlm.nih.gov/30015937/

5. Tao, Yiming, Luo, Jia, Zhu, Hongyi, Chu, Yi, Pei, Lei. 2022. Chromosome 12 Open Reading Frame 49 Promotes Tumor Growth and Predicts Poor Prognosis in Colorectal Cancer. In Digestive diseases and sciences, 68, 1306-1315. doi:10.1007/s10620-022-07751-x. https://pubmed.ncbi.nlm.nih.gov/36348128/