Oncogenic GNAS Uses PKA-Dependent and Independent Mechanisms to Induce Cell Proliferation in Human Pancreatic Ductal and Acinar Organoids.

IF 4.1 2区医学 Q2 CELL BIOLOGY Molecular Cancer Research Pub Date : 2024-05-02 DOI:10.1158/1541-7786.MCR-23-0199

Ridhdhi Desai, Ling Huang, Raul S Gonzalez, Senthil K Muthuswamy

引用次数: 0

Abstract

Implications: The study identifies an opportunity to discover a PKA-independent pathway downstream of oncogene GNAS for managing IPMN lesions and their progression to PDAC.

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致癌基因 GNAS 利用 PKA 依赖性和独立机制诱导人胰腺导管和尖腺器官组织中的细胞增殖。

胰腺导管和针状胰腺器官组织是研究胰腺疾病的理想模型。基因组测序研究发现，G 蛋白（GNASR201C）突变只出现在导管内乳头状黏液性肿瘤（IPMNs）中。GNASR201C影响胰腺导管和尖头外分泌的生物学机制尚不清楚。在这里，我们使用源自人类干细胞的胰腺导管和尖腺器质体，证明与尖腺器质体相比，GNASR201C能更有效地诱导导管器质体增殖。令人惊讶的是，GNASR201C诱导的细胞增殖在导管器官组织和永生导管上皮细胞系中不依赖于蛋白激酶A（PKA）。致癌基因 KRASG12V 和 GNASR201C 的联合表达在导管器官组织中刺激细胞增殖时仍不依赖 PKA。因此，我们确定了 PKA 信号在 GNASR201C 驱动的癌前病变细胞增殖中的细胞系特异性作用，并报告了人类胰腺导管类器官模型系统的开发情况，以研究 GNASR201C 诱导的 IPMNs 的调控机制。意义：该研究为发现癌基因 GNAS 下游独立于 PKA 的通路提供了机会，可用于管理 IPMN 病变及其向 PDAC 的发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Cancer Research 医学-细胞生物学

CiteScore

9.90

自引率

0.00%

发文量

280

审稿时长

4-8 weeks

期刊介绍： Molecular Cancer Research publishes articles describing novel basic cancer research discoveries of broad interest to the field. Studies must be of demonstrated significance, and the journal prioritizes analyses performed at the molecular and cellular level that reveal novel mechanistic insight into pathways and processes linked to cancer risk, development, and/or progression. Areas of emphasis include all cancer-associated pathways (including cell-cycle regulation; cell death; chromatin regulation; DNA damage and repair; gene and RNA regulation; genomics; oncogenes and tumor suppressors; signal transduction; and tumor microenvironment), in addition to studies describing new molecular mechanisms and interactions that support cancer phenotypes. For full consideration, primary research submissions must provide significant novel insight into existing pathway functions or address new hypotheses associated with cancer-relevant biologic questions.