L1td1-KO Mouse

L1TD1, also known as FLJ10884 or ECAT11, is a cytoplasmic RNA-binding protein. It is specifically expressed in pluripotent stem cells and is essential for maintaining stemness in human cells [2,3,4,6]. L1TD1 is involved in post-transcriptional regulation, with roles in RNA splicing, translation, protein traffic, and degradation [3]. It is part of the pluripotency interactome network of OCT4, SOX2, and NANOG, bridging nuclear and cytoplasmic regulation and highlighting the importance of RNA biology in pluripotency [3].

In cancer research, L1TD1 shows different prognostic values in different cancer types. In colon cancer, increased expression of L1TD1 is associated with longer disease-free survival, making it a positive prognostic marker [1]. However, in medulloblastoma, high expression of L1TD1 is linked with poor prognosis. Depletion of L1TD1 in medulloblastoma cells reduces cell viability, inhibits cell proliferation, induces apoptosis, downregulates neural stem cell markers, inhibits neurosphere generation, and sensitizes cells to chemotherapeutic agents [7]. In non-small cell lung cancer (NSCLC), L1TD1 is tumor-specifically methylated, and its DNA methylation is involved in transcriptional regulation. Overexpression of L1TD1 in NSCLC cells shows tumor-cell growth suppressing properties [5].

In conclusion, L1TD1 is crucial for maintaining pluripotency in human cells and has significant implications in cancer. Its role in different cancers varies, as seen from studies in medulloblastoma, colon cancer, and NSCLC. These findings from model-based research, especially in cancer cells, help us understand the biological functions of L1TD1 and its potential as a prognostic marker or therapeutic target in malignant diseases.

References:

1. Chakroborty, Deepankar, Emani, Maheswara Reddy, Klén, Riku, Lahesmaa, Riitta, Elo, Laura L. 2019. L1TD1 - a prognostic marker for colon cancer. In BMC cancer, 19, 727. doi:10.1186/s12885-019-5952-2. https://pubmed.ncbi.nlm.nih.gov/31337362/

2. Jin, Sang Woo, Seong, Youngmo, Yoon, Dayoung, Kwon, Young-Soo, Song, Hoseok. . Dissolution of ribonucleoprotein condensates by the embryonic stem cell protein L1TD1. In Nucleic acids research, 52, 3310-3326. doi:10.1093/nar/gkad1244. https://pubmed.ncbi.nlm.nih.gov/38165001/

3. Emani, Maheswara Reddy, Närvä, Elisa, Stubb, Aki, Elo, Laura L, Lahesmaa, Riitta. 2015. The L1TD1 protein interactome reveals the importance of post-transcriptional regulation in human pluripotency. In Stem cell reports, 4, 519-28. doi:10.1016/j.stemcr.2015.01.014. https://pubmed.ncbi.nlm.nih.gov/25702638/

4. Wong, Raymond Ching-Bong, Ibrahim, Abel, Fong, Helen, Lock, Leslie F, Donovan, Peter J. 2011. L1TD1 is a marker for undifferentiated human embryonic stem cells. In PloS one, 6, e19355. doi:10.1371/journal.pone.0019355. https://pubmed.ncbi.nlm.nih.gov/21559406/

5. Altenberger, Corinna, Heller, Gerwin, Ziegler, Barbara, Zielinski, Christoph C, Zöchbauer-Müller, Sabine. 2017. SPAG6 and L1TD1 are transcriptionally regulated by DNA methylation in non-small cell lung cancers. In Molecular cancer, 16, 1. doi:10.1186/s12943-016-0568-5. https://pubmed.ncbi.nlm.nih.gov/28093071/

6. Närvä, Elisa, Rahkonen, Nelly, Emani, Maheswara Reddy, Rao, Anjana, Lahesmaa, Riitta. . RNA-binding protein L1TD1 interacts with LIN28 via RNA and is required for human embryonic stem cell self-renewal and cancer cell proliferation. In Stem cells (Dayton, Ohio), 30, 452-60. doi:10.1002/stem.1013. https://pubmed.ncbi.nlm.nih.gov/22162396/

7. Santos, Márcia Cristina Teixeira, Silva, Patrícia Benites Gonçalves, Rodini, Carolina Oliveira, Moreira, José C F, Okamoto, Oswaldo Keith. 2015. Embryonic Stem Cell-Related Protein L1TD1 Is Required for Cell Viability, Neurosphere Formation, and Chemoresistance in Medulloblastoma. In Stem cells and development, 24, 2700-8. doi:10.1089/scd.2015.0052. https://pubmed.ncbi.nlm.nih.gov/26159230/