RT Journal Article SR Electronic T1 CDCP1 promotes compensatory renal growth by integrating Src and Met signaling JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e202000832 DO 10.26508/lsa.202000832 VO 4 IS 4 A1 Kentaro Kajiwara A1 Shotaro Yamano A1 Kazuhiro Aoki A1 Daisuke Okuzaki A1 Kunio Matsumoto A1 Masato Okada YR 2021 UL https://www.life-science-alliance.org/content/4/4/e202000832.abstract AB Compensatory growth of organs after loss of their mass and/or function is controlled by hepatocyte growth factor (HGF), but the underlying regulatory mechanisms remain elusive. Here, we show that CUB domain-containing protein 1 (CDCP1) promotes HGF-induced compensatory renal growth. Using canine kidney cells as a model of renal tubules, we found that HGF-induced temporal up-regulation of Src activity and its scaffold protein, CDCP1, and that the ablation of CDCP1 robustly abrogated HGF-induced phenotypic changes, such as morphological changes and cell growth/proliferation. Mechanistic analyses revealed that up-regulated CDCP1 recruits Src into lipid rafts to activate STAT3 associated with the HGF receptor Met, and activated STAT3 induces the expression of matrix metalloproteinases and mitogenic factors. After unilateral nephrectomy in mice, the Met-STAT3 signaling is transiently up-regulated in the renal tubules of the remaining kidney, whereas CDCP1 ablation attenuates regenerative signaling and significantly suppresses compensatory growth. These findings demonstrate that CDCP1 plays a crucial role in controlling compensatory renal growth by focally and temporally integrating Src and Met signaling.