Role of Kindlin 2 in prostate cancer

• Published in: Scientific reports Vol. 14; no. 1; pp. 19809 - 12
• Main Authors: Bialkowska, Katarzyna, El Khalki, Lamyae, Rana, Priyanka S., Wang, Wei, Lindner, Daniel J., Parker, Yvonne, Languino, Lucia R., Altieri, Dario C., Pluskota, Elzbieta, Sossey-Alaoui, Khalid, Plow, Edward F.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.08.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/67; 692/4028; Adapter proteins; Adhesion; Androgen dependence; Androgens; Angiogenesis; Animals; Cell Adhesion; Cell Line, Tumor; Cell migration; Cell Movement; Cell Proliferation; Cell surface; CRISPR; Cytoskeleton; Extracellular matrix; Humanities and Social Sciences; Humans; Integrins; Integrins - metabolism; Kindlin-2; Male; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; multidisciplinary; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Science; Science (multidisciplinary); Testosterone; Therapeutic targets; Tumor angiogenesis; Tumor cell lines; Tumor progression; Tumors; Tumor angiogenesis; Prostate cancer; Tumor progression; Androgen dependence; Kindlin-2; Integrins
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-70202-2

Kindlin-2 is a cytoskeletal adapter protein that is present in many different cell types. By virtue of its interaction with multiple binding partners, Kindlin-2 intercalates into numerous signaling pathways and cytoskeletal nodes. A specific interaction of Kindlin-2 that is of paramount importance in many cellular responses is its direct binding to the cytoplasmic tails of integrins, an interaction that controls many of the adhesive, migratory and signaling responses mediated by members of the integrin family of cell-surface heterodimers. Kindlin-2 is highly expressed in many cancers and is particularly prominent in prostate cancer cells. CRISPR/cas9 was used as a primary approach to knockout expression of Kindlin-2 in both androgen-independent and dependent prostate cancer cell lines, and the effects of Kindlin-2 suppression on oncogenic properties of these prostate cancer cell lines was examined. Adhesion to extracellular matrix proteins was markedly blunted, consistent with the control of integrin function by Kindlin-2. Migration across matrices was also affected. Anchorage independent growth was markedly suppressed. These observations indicate that Kindlin-2 regulates hallmark features of prostate cancer cells. In androgen expressing cells, testosterone-stimulated adhesion was Kindlin-2-dependent. Furthermore, tumor growth of a prostate cancer cell line lacking Kindlin-2 and implanted into the prostate gland of immunocompromised mice was markedly blunted and was associated with suppression of angiogenesis in the developing tumor. These results establish a key role of Kindlin-2 in prostate cancer progression and suggest that Kindlin-2 represents an interesting therapeutic target for treatment of prostate cancer.