Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117594, Singapore.
School of Anatomy, Human Biology and Physiology, University of Western Australia, Crawley, WA, 6009, Australia.
Breast Cancer Res Treat. 2022 Jan;191(1):63-75. doi: 10.1007/s10549-021-06426-x. Epub 2021 Oct 26.
Invasion of carcinoma cells into surrounding tissue affects breast cancer staging, influences choice of treatment, and impacts on patient outcome. KIF21A is a member of the kinesin superfamily that has been well-studied in congenital extraocular muscle fibrosis. However, its biological relevance in breast cancer is unknown. This study investigated the functional roles of KIF21A in this malignancy and examined its expression pattern in breast cancer tissue.
The function of KIF21A in breast carcinoma was studied in vitro by silencing its expression in breast cancer cells and examining the changes in cellular activities. Immunohistochemical staining of breast cancer tissue microarrays was performed to determine the expression patterns of KIF21A.
Knocking down the expression of KIF21A using siRNA in MDA-MB-231 and MCF7 human breast cancer cells resulted in significant decreases in tumor cell migration and invasiveness. This was associated with reduced Patched 1 expression and F-actin microfilaments. Additionally, the number of focal adhesion kinase- and paxillin-associated focal adhesions was increased. Immunohistochemical staining of breast cancer tissue microarrays showed that KIF21A was expressed in both the cytoplasmic and nuclear compartments of carcinoma cells. Predominance of cytoplasmic KIF21A was significantly associated with larger tumors and high grade cancer, and prognostic of cause-specific overall patient survival and breast cancer recurrence.
The data demonstrates that KIF21A is an important regulator of breast cancer aggressiveness and may be useful in refining prognostication of this malignant disease.
癌细胞侵犯周围组织会影响乳腺癌的分期，影响治疗方案的选择，并影响患者的预后。KIF21A 是驱动蛋白超家族的成员，在先天性眼外肌纤维化中已有深入研究。然而，其在乳腺癌中的生物学相关性尚不清楚。本研究旨在探讨 KIF21A 在这种恶性肿瘤中的功能作用，并研究其在乳腺癌组织中的表达模式。
通过沉默乳腺癌细胞中的 KIF21A 表达，并观察细胞活性的变化，在体外研究 KIF21A 在乳腺癌中的功能。通过免疫组织化学染色检测乳腺癌组织微阵列，确定 KIF21A 的表达模式。
用 siRNA 敲低 MDA-MB-231 和 MCF7 人乳腺癌细胞中的 KIF21A 表达，导致肿瘤细胞迁移和侵袭能力显著下降。这与 patched 1 表达和 F- 肌动蛋白微丝减少有关。此外，粘着斑激酶和桩蛋白相关粘着斑的数量增加。免疫组织化学染色检测乳腺癌组织微阵列显示，KIF21A 在癌细胞的细胞质和核质中均有表达。细胞质中 KIF21A 的优势与较大的肿瘤和高级别癌症显著相关，并与特定原因的总患者生存和乳腺癌复发的预后相关。
数据表明，KIF21A 是乳腺癌侵袭性的重要调节因子，可能有助于改善对这种恶性疾病的预后判断。
