Kank3, short for kidney or KN motif and ankyrin repeat domain-containing protein 3, is part of the Kank family. It is essential for crosstalk between actin and microtubules, localizing mainly to the plasma membrane in focal adhesions, indirectly affecting RhoA and Rac1 to regulate the actin cytoskeleton, and is also part of the cortical microtubule stabilisation complex [2]. Kank3 was identified as a hypoxia-inducible pro-apoptotic target of p53 [2].

In lung adenocarcinoma (LUAD), Kank3 is down-regulated, and its expression influences patient prognosis. Overexpression of Kank3 inhibits, while its silencing enhances, the proliferation, invasion, and migration of LUAD cells. It regulates these processes through the p38 MAPK pathway, suggesting it could be a novel therapeutic target for LUAD [1].

In hepatocellular carcinoma (HCC), Kank3 acts as a tumor suppressor in an oxygen-dependent manner. Knockdown of Kank3 in HCC cells enhances cell migration and invasion, while overexpression inhibits these behaviors [3].

In hypopharyngeal squamous cell carcinoma (HSCC), Kank3 is a favorable prognosis marker and is significantly down-regulated in lymphatic metastatic tissues compared with adjacent normal tissues [4].

In lung squamous cell carcinoma (LUSC), pterostilbene exerts anti-LUSC function in a Kank3-inhibition-dependent manner, as re-induction of Kank3 impairs the anti-LUSC effects of pterostilbene [5].

In conclusion, Kank3 plays crucial roles in multiple cancer types, mainly acting as a tumor suppressor. Its functions in regulating cell proliferation, invasion, and migration are revealed through studies in different cancer models. Understanding Kank3 may provide new insights into cancer treatment strategies for diseases such as LUAD, HCC, HSCC, and LUSC.