Open AccessSmall Molecular Inhibitors Reverse Cancer Metastasis by Blockading Oncogenic PITPNM3
Author(s) -
Liu Zihao,
Shi Yu,
Lv Li,
Chen Jianing,
Jiang WenG.,
Li Jun,
Lin Qun,
Fang Xiaolin,
Gao Jingbo,
Liu Yujie,
Liu Qiang,
Xu Xiaoding,
Song Erwei,
Gong Chang
Publication year - 2022
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202204649
Subject(s) - metastasis , cancer metastasis , cancer , breast cancer , cancer research , breast cancer metastasis , cancer cell , metastatic breast cancer , medicine , biology
Most cancer‐related deaths are a result of metastasis. The development of small molecular inhibitors reversing cancer metastasis represents a promising therapeutic opportunity for cancer patients. This pan‐cancer analysis identifies oncogenic roles of membrane‐associated phosphatidylinositol transfer protein 3 (PITPNM3), which is crucial for cancer metastasis. Small molecules targeting PITPNM3 must be explored further. Here, PITPNM3‐selective small molecular inhibitors are reported. These compounds exhibit target‐specific inhibition of PITPNM3 signaling, thereby reducing metastasis of breast cancer cells. Besides, by using nanoparticle‐based delivery systems, these PITPNM3‐selective compounds loaded nanoparticles significantly repress metastasis of breast cancer in mouse xenograft models and organoid models. Notably, the results establish an important metastatic‐promoting role for PITPNM3 and offer PITPNM3 inhibition as a therapeutic strategy in metastatic breast cancer.