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Genes & Devel:揭秘乳腺癌細胞可塑性產生的分子機制

目前治療乳腺癌的一大障礙就是癌細胞會不斷改變方式來對療法產生耐受性,理解介導癌細胞可塑性的細胞機制或能幫助開發新型的乳腺癌療法;近日,一項刊登在國際雜志GenesDevelopment上的研究報告中,來自貝勒醫學院的科學家們通過研究發現,乳腺癌細胞或能在兩

目前治療乳腺癌的一大障礙就是癌細胞會不斷改變方式來對療法產生耐受性,理解介導癌細胞可塑性的細胞機制或能幫助開發新型的乳腺癌療法;近日,一項刊登在國際雜志Genes & Development上的研究報告中,來自貝勒醫學院的科學家們通過研究發現,乳腺癌細胞或能在兩種形式的細胞表面分子之間移動,即CD44分子—CD44s和CD44v;主要表達CD44s的乳腺癌細胞會增加轉移的行為及對療法的耐受性,而主要表達CD44v的癌細胞則會增加癌細胞的增殖特性。

圖片來源:Tom Misteli, Ph.D., and Karen Meaburn, Ph.D. at the NIH IRP.

研究者Chonghui Cheng說道,我們的目標是理解促進乳腺癌細胞變得異質性的分子機制,異質性是癌細胞難以治療的一種原因;文章中,研究人員對乳腺癌干細胞進行了深入研究,這類細胞能夠產生不同特性的細胞,而這種特性主要表現在細胞表面分子CD44上。CD44是癌癥干細胞的一種已知標志物,CD44基因能通過選擇性剪接的方式產生CD44s和CD44v兩種蛋白,研究者調查了這兩種分子在乳腺癌細胞中表達的差異型,他們想知道是否不同形式的CD44分子會引發不同的疾病結果。

文章中,研究者發現,在乳腺癌中,CD44s和CD44v兩種CD44分子具有不同的生物學功能,乳腺癌細胞能利用不同形式的CD44分子,同時還能在兩種CD44分子之間不斷轉換,表達高水平CD44s的癌細胞具有癌癥干細胞的特性,其更趨向于具有轉移性或復發性,而且能對療法產生耐受性;而當其轉換到表達CD44v時,其就會攜帶較少的癌癥干細胞特性,但卻會增加癌細胞的增殖特性,選擇性剪接是一種促進CD44分子轉換的特殊機制。

研究者表示,通過操控兩種CD44分子的水平或許就能改變癌細胞的特性,從而增加癌細胞對療法的敏感性。最后研究者Cheng說道,我們推測,或許還有其它基因也會經歷選擇性剪接的過程從而改變細胞的命運,同時或許還會改變細胞的可塑性從而引發癌癥異質性的發生。

原始出處:

Honghong Zhang, Rhonda L. Brown, Yong Wei, et al. CD44 splice isoform switching determines breast cancer stem cell state, Genes & Development (2019) doi:10.1101/gad.319889.118

 
 
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