{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KIF18B is a member of the kinesin‐8 family that plays multifaceted roles in mitosis and cancer. In normal cells, its expression is tightly regulated in a cell cycle–dependent manner—it is low during interphase (with a predominant nuclear localization) and becomes upregulated in late G2 through metaphase, at which time KIF18B relocalizes along astral microtubules and at microtubule plus ends to control spindle assembly, positioning, and chromosome segregation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Mechanistically, KIF18B modulates microtubule dynamics both directly and through protein–protein interactions. It is capable of binding to microtubule plus ends through its nonmotor C-terminal domain and, in some settings, collaborates with depolymerases such as MCAK—a relationship that is negatively regulated by Aurora kinase–dependent phosphorylation—to promote microtubule depolymerization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, KIF18B contributes to the spatial regulation of microtubule lifetimes near the cell cortex, ensuring proper spindle orientation and, in specialized cells like keratinocytes, influencing asymmetric cell division."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its canonical mitotic functions, KIF18B has emerged as an important oncogenic factor in several tumor types. Elevated expression of KIF18B is frequently observed in cancers such as hepatocellular carcinoma, pancreatic ductal adenocarcinoma, lung adenocarcinoma, breast cancer, prostate cancer, cutaneous melanoma, and colorectal cancer, and its upregulation correlates with increased cell proliferation, enhanced migration and invasion, and poor patient prognosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In prostate cancer models, for example, KIF18B overexpression was shown to activate the PI3K–AKT–mTOR signaling cascade, whereas in colorectal cancer it supports chemoresistance by sustaining PARPBP expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Furthermore, recent findings have uncovered a nuclear role for KIF18B in the repair of DNA double‐strand breaks through an interaction with the repair factor 53BP1, suggesting that beyond its role in spindle dynamics, it may contribute to genome integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these studies establish KIF18B as a multifunctional protein whose coordinated regulation of microtubule dynamics and spindle organization is critical for faithful cell division, while its aberrant expression in tumors contributes to cancer progression and chemoresistance. Its diverse roles in both the cytoplasmic and nuclear compartments make KIF18B a promising diagnostic and therapeutic target across multiple malignancies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Young Mi Lee, Eunjoung Kim, Minjong Park, et al. 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