Epigenetic and Posttranscriptional Modulation of SOS1 Can Promote Breast Cancer Metastasis through Obesity-Activated c-Met Signaling in African-American Women.

ABSTRACT: Ethnicity is considered to be one of the major risk factors in certain subtypes of breast cancer. However, the mechanism of this racial disparity remains poorly understood. Here, we demonstrate that SOS1, a key regulator of Ras pathway, is highly expressed in African-American (AA) patients with breast cancer compared with Caucasian-American patients. Because of the higher obesity rate in AA women, increased levels of SOS1 facilitated signal transduction of the c-Met pathway, which was highly activated in AA patients with breast cancer via hepatocyte growth factor secreted from adipocytes. Elevated expression of SOS1 also enhanced cancer stemness through upregulation of PTTG1 and promoted M2 polarization of macrophages by CCL2 in metastatic sites. SOS1 was epigenetically regulated by a supe

SUBMITTER: Xing F 

PROVIDER: S-EPMC8178187 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature