Limd1-KO Mouse

LIMD1, also known as LIM domains containing 1, is a member of the LIM domain scaffolding proteins. It functions as a tumor suppressor in lung cancer, regulating Hippo-YAP signaling activity [3]. It also plays a role in cell-matrix adhesions, contributing to cellular mechanics and durotaxis by regulating focal adhesion dynamics in response to force [1].

In non-small cell lung cancers (NSCLC), approximately 45% are deficient in LIMD1. LIMD1-deficient NSCLC cells can be selectively targeted by PF-477736, which inhibits multiple kinases and induces apoptosis [2]. In lung adenocarcinoma, overexpressing LIMD1 increases the sensitivity to cisplatin via the GADD45α/p38 MAPK signaling pathway [4]. In non-Hodgkin's lymphoma, silencing of LIMD1 promotes proliferation and reverses cell adhesion-mediated drug resistance [5].

In conclusion, LIMD1 has crucial functions in tumor suppression and cell-matrix adhesion-related processes. Its deficiency or manipulation is associated with various cancer-related phenotypes, highlighting its importance as a potential therapeutic target in multiple cancer types such as NSCLC, lung adenocarcinoma, and non-Hodgkin's lymphoma.

References:

1. Wang, Yuan, Zhang, Chunlei, Yang, Wenzhong, Liang, Ling, Wu, Congying. 2021. LIMD1 phase separation contributes to cellular mechanics and durotaxis by regulating focal adhesion dynamics in response to force. In Developmental cell, 56, 1313-1325.e7. doi:10.1016/j.devcel.2021.04.002. https://pubmed.ncbi.nlm.nih.gov/33891898/

2. Davidson, Kathryn, Grevitt, Paul, Contreras-Gerenas, Maria F, Martin, Sarah A, Sharp, Tyson V. 2021. Targeted therapy for LIMD1-deficient non-small cell lung cancer subtypes. In Cell death & disease, 12, 1075. doi:10.1038/s41419-021-04355-7. https://pubmed.ncbi.nlm.nih.gov/34764236/

3. Zhou, Jiuli, Zhang, Lin, Zhou, Wei, Cheng, Yufeng, Dong, Jixin. 2019. LIMD1 phosphorylation in mitosis is required for mitotic progression and its tumor-suppressing activity. In The FEBS journal, 286, 963-974. doi:10.1111/febs.14743. https://pubmed.ncbi.nlm.nih.gov/30600590/

4. Zeng, Xiaofei, Wang, Hong, He, Dongsheng, Jia, Weikun, Ma, Ruidong. 2020. LIMD1 Increases the Sensitivity of Lung Adenocarcinoma Cells to Cisplatin via the GADD45α/p38 MAPK Signaling Pathway. In Frontiers in oncology, 10, 969. doi:10.3389/fonc.2020.00969. https://pubmed.ncbi.nlm.nih.gov/32754438/

5. Tang, Jie, Zhu, Liqun, Huang, Yuejiao, Wang, Yuchan, Wang, Chun. 2019. Silencing of LIMD1 promotes proliferation and reverses cell adhesion-mediated drug resistance in non-Hodgkin's lymphoma. In Oncology letters, 17, 2993-3000. doi:10.3892/ol.2019.9921. https://pubmed.ncbi.nlm.nih.gov/30854077/