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Investigation Of Phosphoserine Aminotransferase 1 And Its Role In Breast Cancer Progression
Author(s) -
Clem Brian,
Metcalf Stephanie,
Kruer Traci,
Klinge Carolyn
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.811.16
Subject(s) - breast cancer , medicine , metastasis , cancer , surgical oncology , oncology , metastatic breast cancer , triple negative breast cancer , cancer research , tumor progression
Metastasis and endocrine resistance are two factors that complicate therapeutic intervention in breast cancer patients and lead to poorer overall survival. Metastasis is known to be responsible for 90% of cancer related deaths, and is especially prevalent in triple negative breast cancer (TNBC); while endocrine resistance can affect up to 50% of patients diagnosed with estrogen receptor positive breast cancer (ER+BC). Phosphoserine aminotransferase 1 (PSAT1) catalyzes the second step within de novo serine biosynthesis and increased expression of enzymes in this pathway have been linked to progression of breast cancer and poor clinical outcomes. Within our preliminary retrospective analysis of human breast cancer patients, we identified an inverse association with elevated transcript levels and poorer distant metastasis free survival, which, coupled to a previously reported correlation of PSAT1 with response to endocrine therapy in patients with ER+BC, we postulate that PSAT1 contributes to breast cancer progression through promotion of metastasis and/or endocrine resistance. To initially determine relevance for PSAT1, immunohistochemistry was performed to determine PSAT1 expression in human breast cancer patients. We found that PSAT1 expression is increased through breast cancer progression, with highest levels observed within metastatic conditions. To investigate the metastatic contribution of PSAT1, we silenced PSAT1 expression within the triple negative breast cancer cell line (TNBC), MDA‐MB‐231. While suppression of PSAT1 had no effect on proliferation, there was a significant decrease in the motility and invasion of these cells. In addition, decreased PSAT1 substantially inhibited tumor nodule formation following tail‐vein injections of MDA‐MB‐231 cells in vivo . To investigate PSAT1's role in endocrine resistance, we used parental MCF‐7 cells and an endocrine‐resistant derivative cell lines and found that resistant cells exhibited higher PSAT1 expression compared to parental MCF‐7 cells. Lastly, suppression of PSAT1 trended to sensitize the resistant cells to 4‐hydroxytamoxifen treatment. Taken together, these data indicate that PSAT1 may contribute to the progression of human breast cancer via either metastasis or endocrine resistance or both and could potentially serve as a viable target for new therapies. Support or Funding Information Supported by a Research Scholar Grant, RSG‐13‐139‐01 from the American Cancer Society This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .