Small Molecular Inhibitors Reverse Cancer Metastasis by Blockading Oncogenic PITPNM3
Abstract 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 phosphatidylinosito...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-12-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202204649 |
| _version_ | 1798004377513885696 |
|---|---|
| author | Zihao Liu Yu Shi Li Lv Jianing Chen WenG. Jiang Jun Li Qun Lin Xiaolin Fang Jingbo Gao Yujie Liu Qiang Liu Xiaoding Xu Erwei Song Chang Gong |
| author_facet | Zihao Liu Yu Shi Li Lv Jianing Chen WenG. Jiang Jun Li Qun Lin Xiaolin Fang Jingbo Gao Yujie Liu Qiang Liu Xiaoding Xu Erwei Song Chang Gong |
| author_sort | Zihao Liu |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-11T12:23:52Z |
| format | Article |
| id | doaj.art-993f5465e7054b208db2e1bacbf17da8 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-11T12:23:52Z |
| publishDate | 2022-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-993f5465e7054b208db2e1bacbf17da82022-12-22T04:24:02ZengWileyAdvanced Science2198-38442022-12-01935n/an/a10.1002/advs.202204649Small Molecular Inhibitors Reverse Cancer Metastasis by Blockading Oncogenic PITPNM3Zihao Liu0Yu Shi1Li Lv2Jianing Chen3WenG. Jiang4Jun Li5Qun Lin6Xiaolin Fang7Jingbo Gao8Yujie Liu9Qiang Liu10Xiaoding Xu11Erwei Song12Chang Gong13Breast Tumor Center Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou 510120 P. R. ChinaBreast Tumor Center Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou 510120 P. R. ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou 510120 P. R. ChinaBreast Tumor Center Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou 510120 P. R. ChinaCardiff China Medical Research Collaborative School of Medicine Cardiff University Heath Park Cardiff CF14 4XN UKDepartment of Biochemistry Zhongshan School of Medicine Sun Yat‐sen University Guangzhou 510080 P. R. ChinaBreast Tumor Center Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou 510120 P. R. ChinaBreast Tumor Center Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou 510120 P. R. ChinaBreast Tumor Center Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou 510120 P. R. ChinaBreast Tumor Center Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou 510120 P. R. ChinaBreast Tumor Center Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou 510120 P. R. ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou 510120 P. R. ChinaBreast Tumor Center Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou 510120 P. R. ChinaBreast Tumor Center Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou 510120 P. R. ChinaAbstract 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.https://doi.org/10.1002/advs.202204649metastasispan‐cancer analysisPITPNM3small molecular inhibitors |
| spellingShingle | Zihao Liu Yu Shi Li Lv Jianing Chen WenG. Jiang Jun Li Qun Lin Xiaolin Fang Jingbo Gao Yujie Liu Qiang Liu Xiaoding Xu Erwei Song Chang Gong Small Molecular Inhibitors Reverse Cancer Metastasis by Blockading Oncogenic PITPNM3 Advanced Science metastasis pan‐cancer analysis PITPNM3 small molecular inhibitors |
| title | Small Molecular Inhibitors Reverse Cancer Metastasis by Blockading Oncogenic PITPNM3 |
| title_full | Small Molecular Inhibitors Reverse Cancer Metastasis by Blockading Oncogenic PITPNM3 |
| title_fullStr | Small Molecular Inhibitors Reverse Cancer Metastasis by Blockading Oncogenic PITPNM3 |
| title_full_unstemmed | Small Molecular Inhibitors Reverse Cancer Metastasis by Blockading Oncogenic PITPNM3 |
| title_short | Small Molecular Inhibitors Reverse Cancer Metastasis by Blockading Oncogenic PITPNM3 |
| title_sort | small molecular inhibitors reverse cancer metastasis by blockading oncogenic pitpnm3 |
| topic | metastasis pan‐cancer analysis PITPNM3 small molecular inhibitors |
| url | https://doi.org/10.1002/advs.202204649 |
| work_keys_str_mv | AT zihaoliu smallmolecularinhibitorsreversecancermetastasisbyblockadingoncogenicpitpnm3 AT yushi smallmolecularinhibitorsreversecancermetastasisbyblockadingoncogenicpitpnm3 AT lilv smallmolecularinhibitorsreversecancermetastasisbyblockadingoncogenicpitpnm3 AT jianingchen smallmolecularinhibitorsreversecancermetastasisbyblockadingoncogenicpitpnm3 AT wengjiang smallmolecularinhibitorsreversecancermetastasisbyblockadingoncogenicpitpnm3 AT junli smallmolecularinhibitorsreversecancermetastasisbyblockadingoncogenicpitpnm3 AT qunlin smallmolecularinhibitorsreversecancermetastasisbyblockadingoncogenicpitpnm3 AT xiaolinfang smallmolecularinhibitorsreversecancermetastasisbyblockadingoncogenicpitpnm3 AT jingbogao smallmolecularinhibitorsreversecancermetastasisbyblockadingoncogenicpitpnm3 AT yujieliu smallmolecularinhibitorsreversecancermetastasisbyblockadingoncogenicpitpnm3 AT qiangliu smallmolecularinhibitorsreversecancermetastasisbyblockadingoncogenicpitpnm3 AT xiaodingxu smallmolecularinhibitorsreversecancermetastasisbyblockadingoncogenicpitpnm3 AT erweisong smallmolecularinhibitorsreversecancermetastasisbyblockadingoncogenicpitpnm3 AT changgong smallmolecularinhibitorsreversecancermetastasisbyblockadingoncogenicpitpnm3 |