Kank3, short for Kidney or KN motif and ankyrin repeat domain-containing protein 3, is part of the Kank protein family. It is mainly localized to the plasma membrane in focal adhesions, regulating the crosstalk between actin and microtubules. Kank3 indirectly affects RhoA and Rac1, thus regulating the actin cytoskeleton, and is also part of the cortical microtubule stabilisation complex [2].

In lung adenocarcinoma (LUAD), Kank3 was found to be down-regulated in tissues, and its expression influenced patient prognosis. Overexpression of Kank3 inhibited, while its silencing enhanced, the proliferation, invasion, and migration of NCI-H1975 and PC-9 cells. Kank3 regulated LUAD cells' behavior through the p38 MAPK pathway, suggesting it could be a novel therapeutic target [1]. In hepatocellular carcinoma (HCC), Kank3 knockdown enhanced cell migration and invasion, while overexpression inhibited these behaviors, acting as a tumor suppressor in an oxygen-dependent manner [3]. In hypopharyngeal squamous cell carcinoma, Kank3 was significantly down-regulated in lymphatic metastatic tissues compared with adjacent normal tissues, and is a favorable prognosis marker [4]. In lung squamous cell carcinoma, pterostilbene exerted anti-cancer function in a Kank3 inhibition-dependent manner [5].

In summary, Kank3 plays important roles in regulating cell migration, invasion, and proliferation in various cancer types, such as LUAD, HCC, hypopharyngeal squamous cell carcinoma, and lung squamous cell carcinoma. The findings from these studies on Kank3's function in different cancers contribute to understanding its role in tumorigenesis, providing potential directions for cancer treatment.

References:

1. Dai, Ziyu, Xie, Bin, Yang, Baishuang, Hu, Chengping, Chen, Qiong. 2022. KANK3 mediates the p38 MAPK pathway to regulate the proliferation and invasion of lung adenocarcinoma cells. In Tissue & cell, 80, 101974. doi:10.1016/j.tice.2022.101974. https://pubmed.ncbi.nlm.nih.gov/36463587/

2. Tadijan, Ana, Samaržija, Ivana, Humphries, Jonathan D, Humphries, Martin J, Ambriović-Ristov, Andreja. 2020. KANK family proteins in cancer. In The international journal of biochemistry & cell biology, 131, 105903. doi:10.1016/j.biocel.2020.105903. https://pubmed.ncbi.nlm.nih.gov/33309958/

3. Kim, Iljin, Kang, Jengmin, Gee, Heon Yung, Park, Jong-Wan. 2017. A novel HIF1AN substrate KANK3 plays a tumor-suppressive role in hepatocellular carcinoma. In Cell biology international, 42, 303-312. doi:10.1002/cbin.10895. https://pubmed.ncbi.nlm.nih.gov/29047187/

4. Li, Ce, Xu, Chenyang, Guan, Rui, Wei, Dongmin, Lei, Dapeng. 2024. Spatial transcriptomics reveal tumor microenvironment and SLCO2A1 correlated with tumor suppression in hypopharyngeal squamous cell carcinoma. In International immunopharmacology, 142, 113243. doi:10.1016/j.intimp.2024.113243. https://pubmed.ncbi.nlm.nih.gov/39340989/

5. He, Hua, Li, Tian. . Pterostilbene exerts anti-lung squamous cell carcinoma function by suppressing the level of KANK3. In Chemical biology & drug design, 104, e14597. doi:10.1111/cbdd.14597. https://pubmed.ncbi.nlm.nih.gov/39044124/