FAM3C-YY1 axis is essential for TGFβ-promoted proliferation and migration of human breast cancer MDA-MB-231 cells via the activation of HSF1.

Weili Yang,Hongquan Zhang,Junpei Wang,Jichun Yang,Yang Yang,Yuhong Meng,Bin Geng,Biaoqi Feng,Qinghua Cui

doi:10.1111/jcmm.14243

Abstract

Family with sequence similarity three member C (FAM3C) (interleukin‐like EMT inducer [ILEI]), heat shock factor 1 (HSF1) and Ying‐Yang 1 (YY1) have been independently reported to be involved in the pathogenesis of various cancers. However, whether they are coordinated to trigger the development of cancer remains unknown. This study determined the role and mechanism of YY1 and HSF1 in FAM3C‐induced proliferation and migration of breast cancer cells. In human MDA‐MB‐231 breast cancer cell line, transforming growth factor‐β (TGFβ) up‐regulated FAM3C, HSF1 and YY1 expressions. FAM3C overexpression promoted the proliferation and migration of MDA‐MB‐231 cells with YY1 and HSF1 up‐regulation, whereas FAM3C silencing exerted the opposite effects. FAM3C inhibition repressed TGFβ‐induced HSF1 activation, and proliferation and migration of breast cancer cells. YY1 was shown to directly activate HSF1 transcription to promote the proliferation and migration of breast cancer cells. YY1 silencing blunted FAM3C‐ and TGFβ‐triggered activation of HSF1‐Akt‐Cyclin D1 pathway, and proliferation and migration of breast cancer cells. Inhibition of HSF1 blocked TGFβ‐, FAM3C‐ and YY1‐induced proliferation and migration of breast cancer cells. YY1 and HSF1 had little effect on FAM3C expression. Similarly, inhibition of HSF1 also blunted FAM3C‐ and TGFβ‐promoted proliferation and migration of human breast cancer BT‐549 cells. In human breast cancer tissues, FAM3C, YY1 and HSF1 protein expressions were increased. In conclusion, FAM3C activated YY1‐HSF1 signalling axis to promote the proliferation and migration of breast cancer cells. Furthermore, novel FAM3C‐YY1‐HSF1 pathway plays an important role in TGFβ‐triggered proliferation and migration of human breast cancer MDA‐MB‐231 cells.

Highlights

Breast cancer is one malignant tumour that occurs in the breast ep‐ ithelium
heat shock factor 1 (HSF1) overexpression stimulated the proliferation of MDA‐MB‐231 cells, but was re‐ versed by KRIBB11 (Figure S5B‐D). These findings revealed that FAM3C stimulated the proliferation and migration of breast cancer cells by activating HSF1‐Akt pathway
These findings revealed that HSF1 is a direct target gene of YY1, which stimulated the prolifera‐ tion and migration of breast cancer cells by inducing HSF1 expression

Summary

| INTRODUCTION

Breast cancer is one malignant tumour that occurs in the breast ep‐ ithelium. It was reported that breast cancer had become the most common cancer in the female population worldwide in 2012.1 In 2012, about 520 000 people died of breast cancer worldwide.[1]. Heat shock factor 1 (HSF1) is a transcription factor controlling the process of stress, shock response, development and many other bi‐ ological processes by inducing the expression of heat shock proteins (HSPs).[21,22] Heat shock factor 1 is activated in breast cancer tissue, and its high expression level is associated with poor prognosis of breast cancer.[23,24] Clearly, both FAM3C and HSF1 are important biomarkers and potential targets for the diagnosis and treatment of breast cancer Whether they are coordinated to promote the development of breast cancer remains unknown. The role of FAM3C‐HSF1 path‐ way in TGFβ‐induced proliferation and migration of breast cancer cells would be studied

| EXPERIMENTAL PROCEDURE

| DISCUSSION

Findings

CONFLICT OF INTEREST